Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2015, Vol. 6 Issue (4) : 282-299     DOI: 10.14336/AD.2014.002
Review Article |
Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment
Chakrabarti Sasanka1,*, Kumar Khemka Vineet1, Banerjee Anindita1,2, Chatterjee Gargi1, Ganguly Anirban1, Biswas Atanu3
1 Department of Biochemistry, Institute of Post Graduate Medical Education and Research, Kolkata, India.
2 Department of Biochemistry, ICARE Institute of Medical Sciences and Research, Haldia, India.
3 Department of Neuromedicine, Bangur Institute of Neurosciences (BIN), Kolkata, India.
Download: PDF(1071 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    

Alzheimer's disease (AD), the major cause of dementia among the elderly world-wide, manifests in familial and sporadic forms, and the latter variety accounts for the majority of the patients affected by this disease. The etiopathogenesis of sporadic AD is complex and uncertain. The autopsy studies of AD brain have provided limited understanding of the antemortem pathogenesis of the disease. Experimental AD research with transgenic animal or various cell based models has so far failed to explain the complex and varied spectrum of AD dementia. The review, therefore, emphasizes the importance of AD related risk factors, especially those with metabolic implications, identified from various epidemiological studies, in providing clues to the pathogenesis of this complex disorder. Several metabolic risk factors of AD like hypercholesterolemia, hyperhomocysteinemia and type 2 diabetes have been studied extensively both in epidemiology and experimental research, while much less is known about the role of adipokines, pro-inflammatory cytokines and vitamin D in this context. Moreover, the results from many of these studies have shown a degree of variability which has hindered our understanding of the role of AD related risk factors in the disease progression. The review also encompasses the recent recommendations regarding clinical and neuropathological diagnosis of AD and brings out the inherent uncertainty and ambiguity in this area which may have a distinct impact on the outcome of various population-based studies on AD-related risk factors.

Keywords Metabolic      risk factors      sporadic      Alzheimer's disease      pathogenesis      treatment     
Corresponding Authors: Chakrabarti Sasanka   
About author:

present address: Kunming Biomed International, Kunming, Yunnan, 650500, China

Issue Date: 01 August 2015
E-mail this article
E-mail Alert
Articles by authors
Chakrabarti Sasanka
Kumar Khemka Vineet
Banerjee Anindita
Chatterjee Gargi
Ganguly Anirban
Biswas Atanu
Cite this article:   
Chakrabarti Sasanka,Kumar Khemka Vineet,Banerjee Anindita, et al. Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment[J]. Aging and disease, 2015, 6(4): 282-299.
URL:     OR
Figure 1.  Risk factors of Alzheimer's disease. Gene -environment interactions may be the underlying mechanism of sporadic AD. Environmental risk factors include those present in external environment or extra-genetic internal milieu of the body. The risk factors may affect the functions of AD-related genes or their regulatory regions by methylation, oxidation or other mechanisms. Gene polymorphisms, on the other hand, may aggravate the effects of the risk factors on AD pathogenesis. Drugs, diet and life-style may prevent the interaction of risk factors with AD pathogenic mechanisms.
Figure 1.  Metabolic risk factors and molecular pathogenesis of AD. AD pathogenesis is represented by interacting damage pathways spearheaded by soluble oligomers of amyloid beta peptide. Altered levels of metabolic risk factors e.g. hormones, vitamins, cytokines, metabolites etc. can affect APP expression and processing or intracellular trafficking, catabolism and clearance of amyloid beta peptide or induce oxidative stress or inflammatory response through interactions at multiple sites leading to neurodegeneration and characteristic proteinopathy of AD. ER-TGN, Endoplasmic reticulum trans- golgi network; BACE, Beta-site APP cleaving enzyme; IDE, Insulin degrading enzyme; LRP, Low density lipoprotein receptor related protein; NT, Neurotransmitter.
[1] Reitz C, Brayne C, Mayeux R (2011). Epidemiology of Alzheimer disease, Nat Rev Neurol, 7:137-152.
[2] Duthey B (2013). Background Paper 6.11. Alzheimer Disease and other Dementias. 6.11: 4-74.
[3] van der Flier WM, Scheltens P (2005). Epidemiology and risk factors of dementia, J Neurol Neurosurg Psychiatry, 76:v2-7.
[4] Bird TD(2012). Early-onset familial Alzheimer disease. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong CT, Smith RJH, Stephens K, editors. Gene Reviews. Seattle: NCBI, 1-17.
[5] Swerdlow RH (2007). Pathogenesis of Alzheimer's disease. Clin Interv Aging. 2:347-359.
[6] Armstrong RA (2011). The pathogenesis of Alzheimer's disease: a reevaluation of the "amyloid cascade hypothesis". Int J Alzheimers Dis, 2011:630865.
[7] Elder GA, Gama Sosa MA, De Gasperi R (2010). Transgenic mouse models of Alzheimer's disease. Mt Sinai J Med, 77:69-81.
[8] Mattson MP (2004). Pathways towards and away from Alzheimer’s Disease. Nature, 430:631-639.
[9] Lahiri DK, Maloney B, Zawia NH (2009). The LEARn model: an epigenetic explanation for idiopathic neurobiological diseases. Mol Psychiatry, 14:992-1003.
[10] Lahiri DK, Maloney B, Basha MR, Ge YW, Zawia NH (2007). How and when environmental agents and dietary factors affect the course of Alzheimer's disease: the "LEARn" model (latent early-life associated regulation) may explain the triggering of AD. Curr Alzheimer Res, 4:219-228.
[11] Lahiri DK, Maloney B (2010). The "LEARn" (Latent Early-life Associated Regulation) model integrates environmental risk factors and the developmental basis of Alzheimer's disease, and proposes remedial steps. Exp Gerontol, 45:291-296.
[12] McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology, 34:939-944.
[13] Forstl H, Kurz A (1999).Clinical features of Alzheimer's disease. Eur Arch Psychiatry Clin Neurosci, 249:288-290.
[14] Geldmacher DS, Whitehouse Jr. PJ (1997). Differential diagnosis of Alzheimers disease. Neurology, 48 Suppl 6: 2S-9S.
[15] Pimmentel EML (2009). Role of neuropsychological assessment in the differential diagnosis of Alzheimer’s disease and vascular dementia. Dement Neuropsychol, 3:214-221.
[16] de la Torre JC (2002).Alzheimer disease as a vascular disorder: nosological evidence. Stroke, 33:1152-1162.
[17] Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AMet al. (2011). Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement, 7:280-292.
[18] Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC,et al. (2011). The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement, 7:270-279.
[19] McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CHet al.(2011).The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement, 7:263-269.
[20] Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MCet al.(2012).National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement., 8:1-13.
[21] Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT (2011). Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect, 1:a006189.
[22] Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW,et al. (2012). National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach. Acta Neuropathol, 123:1-11.
[23] Khachaturian ZS (1985). Diagnosis of Alzheimer's Disease. Arch Neurol, 42: 1097-1105.
[24] Joachim CL, Morris JH, Selkoe DJ (1988). Clinically diagnosed Alzheimer's disease: autopsy results in 150 cases. Ann Neurol, 24:50-56.
[25] Hyman BT, Trojanowski JQ (1997). Editorial on Consensus Recommendations for the post-mortem Diagnosis of Alzheimer Disease from the National Institute on Aging and the Reagan Institute Working Group on Diagnostic Criteria for the neuropathological assessment of Alzheimer Disease. J Neuropathol Exp Neurol, 56:1095-1097.
[26] Serrano-Pozo A, Qian J, Monsell SE, Frosch MP, Betensky RA, Hyman BT (2013). Examination of the clinicopathologic continuum of Alzheimer disease in the autopsy cohort of the National Alzheimer Coordinating Center. J Neuropathol Exp Neurol, 72: 1182-1192.
[27] Nelson PT, Alafuzoff I, Bigio EH, Bouras C, Braak H, Cairns NJ,et al. (2012). Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol, 71:362-381.
[28] Dong S, Duan Y, Hu Y, Zhao Z (2012). Advances in the pathogenesis of Alzheimer's disease: a re-evaluation of amyloid cascade hypothesis. Transl Neurodegener, 1:1-18.
[29] Haass C, Kaether C, Thinakaran G, Sisodia S (2012). Trafficking and proteolytic processing of APP. Cold Spring Harb Perspect Med, 2:a006270.
[30] Suh YH, Checler F (2002). Amyloid precursor protein, presenilins, and alpha-synuclein: molecular pathogenesis and pharmacological applications in Alzheimer's disease. Pharmacol Rev, 54:469-525.
[31] Bali J, Gheinani AH, Zurbriggen S, Rajendran L (2012). Role of genes linked to sporadic Alzheimer's disease risk in the production of β-amyloid peptides. Proc Natl Acad Sci USA, 109:15307-15311.
[32] Iqbal K, Liu F, Gong CX, Grundke-Iqbal I (2010). Tau in Alzheimer disease and related tauopathies. Curr Alzheimer Res, 7:656-664.
[33] Johnson GV, Stoothoff WH (2004).Tau phosphorylation in neuronal cell function and dysfunction. J Cell Sci, 117:5721-5729.
[34] Butterfield DA, Perluigi M, Sultana R (2006). Oxidative stress in Alzheimer's disease brain: new insights from redox proteomics. Eur J Pharmacol, 545:39-50.
[35] Zhao Y, Zhao B (2013). Oxidative stress and the pathogenesis of Alzheimer's disease. Oxid Med Cell Longev, 2013:316523.
[36] Chakrabarti S, Sinha M, Thakurta IG, Banerjee P, Chattopadhyay M (2013). Oxidative stress and amyloid beta toxicity in Alzheimer's disease: intervention in a complex relationship by antioxidants. Curr Med Chem, 20: 4648-4664.
[37] Santos RX, Correia SC, Wang X, Perry G, Smith MA, Moreira PI,et al. (2010). A synergistic dysfunction of mitochondrial fission/fusion dynamics and mitophagy in Alzheimer’s disease. J Alzheimers Dis, 20: S401-S412.
[38] Devi L, Prabhu BM, Galati DF, Avadhani NG, Anandatheerthavarada HK (2010). Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer's disease brain is associated with mitochondrial dysfunction. J Neurosci, 26:9057-9068.
[39] Zotova E, Nicoll JA, Kalaria R, Holmes C, Boche D (2010). Inflammation in Alzheimer's disease: relevance to pathogenesis and therapy. Alzheimers Res Ther, 2:1.
[40] Wyss-Coray T, Rogers J (2012). Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. Cold Spring Harb Perspect Med, 2:a006346.
[41] Salminen A, Ojala J, Suuronen T, Kaarniranta K, Kauppinen A (2008). Amyloid-beta oligomers set fire to inflammasomes and induce Alzheimer's pathology. J Cell Mol Med, 12:2255-2262.
[42] Liu L, Chan C (2014). The role of inflammasome in Alzheimer's disease. Ageing Res Rev, 15:6-15.
[43] Mosconi L, Pupi A, De Leon MJ (2008). Brain glucose hypometabolism and oxidative stress in preclinical Alzheimer's disease. Ann N Y Acad Sci, 1147:180-195.
[44] Mamelak M (2012). Sporadic Alzheimer's disease: the starving brain. J Alzheimers Dis, 31:459-474.
[45] Erol A (2008). An integrated and unifying hypothesis for the metabolic basis of sporadic Alzheimer's disease. J Alzheimers Dis, 13:241-253.
[46] de la Monte SM, Tong M (2014). Brain metabolic dysfunction at the core of Alzheimer's disease. Biochem Pharmacol, 88:548-559.
[47] Besser LM, Gill DP, Monsell SE, Brenowitz W, Meranus DH, Kukull W,et al. (2014). Body mass index, weight change, and clinical progression in mild cognitive impairment and Alzheimer disease. Alzheimer Dis Assoc Disord, 28:36-43.
[48] Gillette-Guyonnet S, Nourhashemi F, Andrieu S, de Glisezinski I, Ousset PJ, Riviere D,et al. (2000). Am J Clin Nutr, 71:637S-642S.
[49] Khemka VK, Bagchi D, Bandyopadhyay K, Bir A, Chattopadhyay M, Biswas A,et al. (2014). Altered serum levels of adipokines and insulin in probable Alzheimer's disease. J Alzheimers Dis, 41:525-533.
[50] Cunnane S, Nugent S, Roy M, Courchesne-Loyer A, Croteau E, Tremblay S,et al. (2011). Brain fuel metabolism, aging, and Alzheimer's disease. Nutrition, 27:3-20.
[51] Gibson GE1, Sheu KF, Blass JP (1998). Abnormalities of mitochondrial enzymes in Alzheimer disease. J Neural Transm, 105:855-870.
[52] Mustafa S, Kutlu U, Tunahan Ç (2014). Systematic analysis of transcription-level effects of neurodegenerative diseases on human brain metabolism by a newly reconstructed brain-specific metabolic network. FEBS Open Bio, In press.
[53] Newington JT, Harris RA, Cumming RC (2013). Reevaluating metabolism in Alzheimer’s disease from the perspective of the astrocyte-neuron lactate shuttle model. J Neurodeg Dis, 2013: 234572.
[54] Frisardi V, Solfrizzi V, Seripa D, Capurso C, Santamato A, Sancarlo D (2010). Metabolic-cognitive syndrome: a cross-talk between metabolic syndrome and Alzheimer's disease. Ageing Res Rev, 9:399-417.
[55] Crean S, Ward A, Mercaldi CJ, Collins JM, Cook MN, Baker NL,et al. (2011). Apolipoprotein E ε4 prevalence in Alzheimer's disease patients varies across global populations: a systematic literature review and meta-analysis. Dement Geriatr Cogn Disord, 31:20-30.
[56] 56. Evans RM, Hui S, Perkins A, Lahiri DK, Poirier J and Farlow MR (2004). Cholesterol and APOE genotype interact to influence Alzheimer disease progression. Neurology, 62:1869-1871.
[57] 57. Kamboh MI, Demirci FY, Wang X, Minster RL, Carrasquillo MM, Pankratz VS,et al. (2012). Genome-wide association study of Alzheimer's disease. Transl Psychiatry, 2:e117.
[58] 58. Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K,et al. (2001). Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ, 322:1447-1451.
[59] Solomon A, Kivipelto M, Wolozin B, Zhou J, Whitmer RA (2009). Midlife serum cholesterol and increased risk of Alzheimer's and vascular dementia three decades later. Dement Geriatr Cogn Disord, 28:75-80.
[60] Evans RM, Emsley CL, Gao S, Sahota A, Hall KS, Farlow MR,et al (2000). Serum cholesterol, APOE genotype, and the risk of Alzheimer's disease: a population-based study of African Americans. Neurology, 54:240-242.
[61] Shepardson NE, Shankar GM, Selkoe DJ (2011). Cholesterol level and statin use in Alzheimer disease: I. Review of epidemiological and preclinical studies. Arch Neurol, 68:1239-1244.
[62] Ramdane S, Daoudi-Gueddah D (2011). Mild hypercholesterolemia, normal plasma triglycerides, and normal glucose levels across dementia staging in Alzheimer's disease: a clinical setting-based retrospective study. Am J Alzheimers Dis Other Demen, 26:399-405.
[63] Paragh G, Balla P, Katona E, Seres I, Egerházi A, Degrell I (2002). Serum paraoxonase activity changes in patients with Alzheimer's disease and vascular dementia. Eur Arch Psychiatry Clin Neurosci, 252:63-67.
[64] Mielke MM, Zandi PP, Shao H, Waern M, Östling S, Guo X,et al. (2010). The 32-year relationship between cholesterol and dementia from midlife to late life. Neurology, 75:1888-1895.
[65] Cedazo-Mínguez A, Ismail MA, Mateos L (2011). Plasma cholesterol and risk for late-onset Alzheimer's disease. Expert Rev Neurother, 11:495-498.
[66] Mielke MM, Zandi PP, Sjögren M, Gustafson D, Ostling S, Steen Bet al. (2005). High total cholesterol levels in late life associated with a reduced risk of dementia. Neurology, 64:1689-1695.
[67] Wolozin B, Kellman W, Ruosseau P, Celesia GG, Siegel G (2000). Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol, 57:1439-1443.
[68] Scott HD, Laake K (2001). Statins for the prevention of Alzheimer's disease. Cochrane Database Syst Rev, 4: CD003160.
[69] Shepardson NE, Shankar GM, Selkoe DJ (2011). Cholesterol level and statin use in Alzheimer disease: II. Review of human trials and recommendations. Arch Neurol, 68:1385-1392.
[70] Wolozin B (2001). A fluid connection: cholesterol and Abeta. Proc Natl Acad Sci USA, 98:5371-5373.
[71] Puglielli L, Tanzi RE, Kovacs DM (2003). Alzheimer's disease: the cholesterol connection. Nat Neurosci. 6:345-351.
[72] Umeda T, Tomiyama T, Kitajima E, Idomoto T, Nomura S, Lambert MP,et al. (2012). Hypercholesterolemia accelerates intraneuronal accumulation of Aβ oligomers resulting in memory impairment in Alzheimer's disease model mice. Life Sci, 91:1169-1176.
[73] Bjorkhem I, Meaney S (2004). Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol, 24:806-815.
[74] Dietschy JM, Turley SD (2001). Cholesterol metabolism in the brain. Curr Opin Lipidol, 12:105-112.
[75] Simons M, Keller P, Dichgans J, Schulz JB (2001). Cholesterol and Alzheimer's disease: is there a link? Neurology, 57:1089-1093.
[76] Michikawa M, Fan QW, Isobe I, Yanagisawa K (2000). Apolipoprotein E exhibits isoform-specific promotion of lipid efflux from astrocytes and neurons in culture. J Neurochem, 74:1008-1016.
[77] Evans RM, Hui S, Perkins A, Lahiri DK, Poirier J, Farlow MR (2004). Cholesterol and APOE genotype interact to influence Alzheimer disease progression. Neurology, 62:1869-1871.
[78] Zuliani G, Donnorso MP, Bosi C, Passaro A, Dalla Nora E, Zurlo A,et al. (2011). Plasma 24S-hydroxycholesterol levels in elderly subjects with late onset Alzheimer's disease or vascular dementia: a case-control study. BMC Neurol, 11:121.
[79] Vega GL, Weiner MF, Lipton AM, Von Bergmann K, Lutjohann D, Moore C,et al. (2003). Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease. Arch Neurol, 60:510-515.
[80] Leibson CL, Rocca WA, Hanson VA, Cha R, Kokmen E, O'Brien PC,et al. (1997). Risk of dementia among persons with diabetes mellitus: a population-based cohort study. Am J Epidemiol, 145:301-308.
[81] Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM (1999). Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology, 53:1937-1942.
[82] Brayne C, Gill C, Huppert FA, Barkley C, Gehlhaar E, Girling DM,et al. (1998). Vascular risks and incident dementia: results from a cohort study of the very old. Dement Geriatr Cogn Disord, 9:175-180.
[83] Peila R, Rodriguez BL, Launer LJ (2002). Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: the Honolulu-Asia aging study. Diabetes, 51:1256-1262.
[84] Li L, Holscher C (2007). Common pathological processes in Alzheimer disease and type 2 diabetes: a review. Brain Res Rev, 56:384-402.
[85] Luchsinger JA, Tang MX, Shea S, Mayeux R (2004). Hyperinsulinemia and risk of Alzheimer disease. Neurology, 63:1187-92.
[86] Luchsinger JA, Reitz C, Honig LS, Tang MX, Shea S, Mayeux R (2005). Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology, 65:545-551.
[87] Cheng G, Huang C, Deng H, Wang H (2012). Diabetes as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies. Intern Med J, 42:484-491.
[88] Exalto LG, Whitmer RA, Kappele LJ, Biessels GJ (2012). An update on type 2 diabetes, vascular dementia and Alzheimer's disease. Exp Gerontol, 47:858-864.
[89] Vagelatos NT, Eslick GD (2013). Type 2 diabetes as a risk factor for Alzheimer's disease: The confounders, interactions, and neuropathology associated with this relationship. Epidemiol Rev, 35:152-160.
[90] Luchsinger JA (2010). Diabetes, related conditions, and dementia. J Neurol Sci, 299:35-38.
[91] Kuusisto J, Koivisto K, Mykkanen L, Helkala EL, Vanhanen M, Hanninen T,et al. (1997). Association between features of the insulin resistance syndrome and Alzheimer's disease independently of apolipoprotein E4 phenotype: cross sectional population based study. BMJ, 315:1045-1049.
[92] Biessels GJ, Strachan MW, Visseren FL, Kappelle LJ, Whitmer RA (2014). Dementia and cognitive decline in type 2 diabetes and prediabetic stages: towards targeted interventions. Lancet Diabetes Endocrinol, 2:246-255.
[93] Reijmer YD, van den Berg E, Ruis C, Kappelle LJ, Biessels GJ (2010). Cognitive dysfunction in patients with type 2 diabetes. Diabetes Metab Res Rev, 26:507-519.
[94] McCrimmon RJ, Ryan CM, Frier BM (2012). Diabetes and cognitive dysfunction. Lancet, 379:2291-2299.
[95] Heitner J, Dickson D (1997). Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects. A retrospective post-mortem immunocytochemical and histofluorescent study. Neurology, 49:1306-1311.
[96] Ahtiluoto S, Polvikoski T, Peltonen M, Solomon A, Tuomilehto J, Winblad Bet al (2010). Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology, 75:1195-1202.
[97] Neumann KF, Rojo L, Navarrete LP, Farias G, Reyes P, Maccioni RB (2008). Insulin resistance and Alzheimer's disease: molecular links & clinical implications.Curr Alzheimer Res, 5:438-447.
[98] De Felice FG (2013). Alzheimer's disease and insulin resistance: translating basic science into clinical applications. J Clin Invest, 123:531-539.
[99] Gasparini L, Gouras GK, Wang R, Gross RS, Beal MF, Greengard P,et al (2001). Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. J Neurosci, 21:2561-2570.
[100] Son SM, Song H, Byun J, Park KS, Jang HC, Park YJ, Mook-Jung I (2012). Altered APP processing in insulin-resistant conditions is mediated by autophagosome accumulation via the inhibition of mammalian target of rapamycin pathway. Diabetes, 61:3126-3138.
[101] Correia SC, Santos RX, Carvalho C, Cardoso S, Candeias E, Santos MS,et al (2012). Insulin signaling, glucose metabolism and mitochondria: major players in Alzheimer's disease and diabetes interrelation. Brain Res, 1441:64-78.
[102] Yang Y, Song W (2013). Molecular links between Alzheimer's disease and diabetes mellitus. Neuroscience, 250: 140-150.
[103] Tang J, Pei Y, Zhou G (2013). When aging-onset diabetes is coming across with Alzheimer disease: comparable pathogenesis and therapy. Exp Gerontol, 48:744-750.
[104] Liu Y, Liu F, Grundke-Iqbal I, Iqbal K, Gong CX (2011). Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes. J. Pathol, 225:54-62.
[105] Frolich L, Blum-Degen D, Bernstein HG, Engelsberger S, Humrich J, Laufer S,et al. (1998). Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. J Neural Transm, 105:423-438.
[106] Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, de la Monte SM (2005). Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer'sdisease: link to brain reductions in acetylcholine. J Alzheimers Dis, 8:247-268.
[107] Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R,et al. (2005). Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes? J Alzheimers Dis. 7:63-80.
[108] Grunblatt E, Salkovic-Petrisic M, Osmanovic J, Riederer P, Hoyer S (2007). Brain insulin system dysfunction in streptozotocin intracerebroventricularly treated rats generates hyperphosphorylated tau protein. J Neurochem, 101: 757-770.
[109] Ho L, Qin W, Pompl PN, Xiang Z, Wang J, Zhao Z,et al. (2004). Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer's disease. FASEB J, 18:902-904.
[110] Park SA (2011). A common pathogenic mechanism linking type-2 diabetes and Alzheimer's disease: evidence from animal models. J Clin Neurol, 7:10-18.
[111] Wallum BJ, Taborsky GJ Jr, Porte D Jr, Figlewicz DP, Jacobson L, Beard JC,et al. (1987). Cerebrospinal fluid insulin levels increase during intravenous insulin infusions in man. J Clin Endocrinol Metab, 64:190-194.
[112] Bosco D, Fava A, Plastino M, Montalcini T, Pujia A (2011). Possible implications of insulin resistance and glucose metabolism in Alzheimer's disease pathogenesis. J Cell Mol Med, 15:1807-1821.
[113] Freiherr J, Hallschmid M, Frey WH 2nd, Brünner YF, Chapman CD, Holscher C,et al. (2013). Intranasal insulin as a treatment for Alzheimer's disease: a review of basic research and clinical evidence. CNS Drugs, 27:505-514.
[114] Williamson R, McNeilly A, Sutherland C (2012). Insulin resistance in the brain: an old-age or new-age problem? Biochem Pharmacol, 84:737-745.
[115] Ciaccio M, Bellia C (2010). Hyperhomocysteinemia and cardiovascular risk: effect of vitamin supplementation in risk reduction. Curr Clin Pharmacol, 5:30-36.
[116] Maron BA, Loscalzo J (2009). The treatment of hyperhomocysteinemia. Annu Rev Med. 60:39-54.
[117] Zhuo JM, Wang H, Pratico D (2011). Is hyperhomocysteinemia an Alzheimer's disease (AD) risk factor, an AD marker, or neither? Trends Pharmacol Sci, 32:562-571.
[118] Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB,et al. (2002). Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med, 346:476-483.
[119] Zylberstein DE, Lissner L, Björkelund C, Mehlig K, Thelle DS, Gustafson D,et al (2009). Midlife homocysteine and late-life dementia in women. A prospective population study. Neurobiol Aging, 32:380-386.
[120] Elias MF, Sullivan LM, D'Agostino RB, Elias PK, Jacques PF, Selhub J,et al. (2005). Homocysteine and cognitive performance in the Framingham offspring study: age is important. Am J Epidemiol, 162:644-653.
[121] Wald DS, Kasturiratne A, Simmonds M (2011). Serum homocysteine and dementia: meta-analysis of eight cohort studies including 8669 participants. Alzheimers Dement. 7:412-417.
[122] Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM (1998). Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol, 55:1449-1455.
[123] Mizrahi EH, Bowirrat A, Jacobsen DW, Korczyn AD, Traore F, Petot GJ,et al. (2004). Plasma homocysteine, vitamin B12 and folate in Alzheimer's patients and healthy Arabs in Israel. J Neurol Sci, 227:109-113.
[124] Postiglione A, Milan G, Ruocco A, Gallotta G, Guiotto G, Di Minno G (2001). Plasma folate, vitamin B(12), and total homocysteine and homozygosity for the C677T mutation of the 5,10-methylene tetrahydrofolate reductase gene in patients with Alzheimer's dementia. A case-control study. Gerontology, 47:324-329.
[125] Nilsson K, Gustafson L, Hultberg B (2012). Elevated plasma homocysteine level is not primarily related to Alzheimer's disease. Dement Geriatr Cogn Disord, 34:121-127.
[126] Seshadri S (2006). Elevated plasma homocysteine levels: risk factor or risk marker for the development of dementia and Alzheimer's disease? J Alzheimers Dis, 9:393-398.
[127] Aisen PS, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, Weiner MF,et al. (2008). High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA, 300: 1774-1783.
[128] Sun Y, Lu CJ, Chien KL, Chen ST, Chen RC (2007). Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients. Clin Ther, 29:2204-2214.
[129] Miller JW, Green R, Mungas DM, Reed BR, Jagust WJ (2006). Homocysteine, vitamin B6, and vascular disease in AD patients. Neurology, 58:1471-1475.
[130] Ray L, Khemka VK, Behera P, Bandyopadhyay K, Pal S, Pal K,et al. (2013).Serum homocysteine, dehydroepiandrosterone sulphate and lipoprotein (a) in Alzheimer's disease and vascular dementia. Aging Dis, 4:57-64.
[131] Obeid R, Herrmann W (2006). Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett, 580:2994-3005.
[132] Lin N, Qin S, Luo S, Cui S, Huang G, Zhang X (2014). Homocysteine induces cytotoxicity and proliferation inhibition in neural stem cells via DNA methylation in vitro. FEBS J, 281:2088-2096.
[133] Kim WK, Pae YS (1996). Involvement of N-methyl-d-aspartate receptor and free radical in homocysteine-mediated toxicity on rat cerebellar granule cells in culture. Neurosci Lett, 216:117-120.
[134] Chandran M, Phillips SA, Ciaraldi T, Henry RR (2003). Adiponectin: more than just another fat cell hormone? Diabetes Care, 26:2442-2450.
[135] Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S,et al. (2002). Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med, 8:1288-1295.
[136] Soodini GR (2004). Adiponectin and leptin in relation to insulin sensitivity. Metab Syndr Relat Disord, 2:114-123.
[137] Thundyil J, Pavlovski D, Sobey CG, Arumugam TV (2012). Adiponectin receptor signalling in the brain. Br J Pharmacol, 165:313-327.
[138] 138. Morton GJ (2007). Hypothalamic leptin regulation of energy homeostasis and glucose metabolism. J Physiol, 583:437-443.
[139] Marwarha G, Ghribi O (2012). Leptin signaling and Alzheimer's disease. Am J Neurodegener Dis, 1:245-265.
[140] Lee EB (2011). Obesity, leptin, and Alzheimer's disease. Ann N Y Acad Sci, 1243:15-29.
[141] Lieb W, Beiser AS, Vasan RS, Tan ZS, Au R, Harris TB,et al. (2009). Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging. JAMA, 302:2565-2572.
[142] Holden KF, Lindquist K, Tylavsky FA, Rosano C, Harris TB, Yaffe K (2009). Serum leptin level and cognition in the elderly: Findings from the Health ABC Study. Neurobiol Aging, 30:1483-1489.
[143] Rizoulis AA, Karaoulanis SE, Rizouli KA, Papadimitriou A (2005). Serum leptin levels in patients with Alzheimer’s disease. Int J Caring Sci, 5:43-49.
[144] Une K, Takei YA, Tomita N, Asamura T, Ohrui T, Furukawa K,et al. (2011). Adiponectin in plasma and cerebrospinal fluid in MCI and Alzheimer's disease. Eur J Neurol, 18:1006-1009.
[145] van Himbergen TM, Beiser AS, Ai M, Seshadri S, Otokozawa S, Au R,et al. (2012). Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and alzheimer disease: results from the Framingham Heart Study. Arch Neurol, 69:594-600.
[146] Warren MW, Hynan LS, Weiner MF (2012). Lipids and adipokines as risk factors for Alzheimer's disease. J Alzheimers Dis, 29:151-157.
[147] Tezapsidis N, Johnston JM, Smith MA, Ashford JW, Casadesus G, Robakis NK,et al. (2009). Leptin: A novel therapeutic strategy for Alzheimer's disease. J Alzheimers Dis, 16:731-740.
[148] Smith JA, Das A, Ray SK, Banik NL (2012). Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain res bull, 87:10-20.
[149] Enciu AM, Popescu BO (2013). Is there a causal link between Inflammation and dementia? Biomed Res Int, 2013:316495.
[150] Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM,et al. (2000). Inflammation and Alzheimer’s disease. Neurobiol Aging, 21:383-421.
[151] Weisman D, Hakimian E,Ho GJ (2006). Interleukins, inflammation, and mechanisms of Alzheimer’s disease. Vitam Horm, 74:505-530.
[152] Rubio-Perez JM and Morillas-Ruiz JM (2012). A review: Inflammatory process in Alzheimer’s disease, Role of cytokines. Scientific World Journal, 2012: 756357.
[153] Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A,et al. (2013). NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature, 493:674-678.
[154] Tan MS, Yu JT, Jiang T, Zhu XC, Tan L (2013). The NLRP3 inflammasome in Alzheimer's disease. Mol Neurobiol, 48:875-882.
[155] Licastro F, Pedrini S, Caputo L, Annoni G, Grimaldi LME (2000). Increased plasma levels of interleukin-1, interleukin-6 and α-1-antichymotrypsin in patients with Alzheimer’s disease: peripheral inflammation or signals from the brain? J Neuroimmunol, 103:97-102.
[156] Mraka RE, Griffin WST (2005). Potential Inflammatory biomarkers in Alzheimer’s disease. J Alzheimers Dis, 8:369-375.
[157] Lee KS, Chung JH, Choi TK, Suh SY, Oh BH, Hong CH (2009). Peripheral cytokines and chemokines in Alzheimer’s disease. Dement Geriatr Cogn Disord, 28:281-287.
[158] Lanzrein A, Johnston CM, Perry VH, Jobst KA, King EM, Smith AD (1998). Longitudinal study of inflammatory factors in serum, cerebrospinal fluid, and brain tissue in Alzheimer disease: interleukin-1β, interleukin-6, interleukin-1 receptor antagonist, tumor necrosis factor-α, the soluble tumor necrosis factor receptors I and II, and α1 antichymotrypsin. Alzheimer Dis Assoc Disord, 12: 215-227.
[159] Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J,Herrmann N (2010). A meta-analysis of cytokines in Alzheimer’s disease. Biol Psychiatry, 68:930-941.
[160] Khemka VK, Ganguly A, Bagchi D, Ghosh A, Bir A, Biswas A,et al. (2014). Raised serum proinflammatory cytokines in Alzheimer's disease with depression. Aging Dis, 5:170-176.
[161] Banks WA, Farr SA, Morley JE (2002). Entry of Blood-Borne Cytokines into the Central Nervous System: Effects on Cognitive Processes. Neuroimmunomodulation, 10:319-327.
[162] Vitkovic L, Konsman JP, Bockaert J, Dantzer R, Homburger V, Jacque C (2000). Cytokine signals propagate through the brain. Mol Psychiatry, 5:604-615.
[163] McAfoose J, Baune BT (2009). Evidence for a cytokine model of cognitive function. Neurosci Biobehav Rev, 33:355-366.
[164] Godbout JP, Chen J, Abraham J, Richwine AF, Berg BM, Kelley KW,et al. (2005). Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system. FASEB J, 19:1329-1331.
[165] Kelley KW, Bluthe RM, Dantzer R, Zhou JH, Shen WH, Johnson RW,et al. (2003). Cytokine-induced sickness behavior. Brain Behav Immun, 17 Suppl 1:S112-118.
[166] Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A,et al. (2001). Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry, 58:445-452.
[167] Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW (2008). From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci, 9:46-56.
[168] Galic MA, Riazi K, Pittman QJ (2012). Cytokines and brain excitability. Front Neuroendocrinol, 33:116-125.
[169] Shaftel SS, Griffin WS, O'Banion MK (2008). The role of interleukin-1 in neuroinflammation and Alzheimer disease: an evolving perspective. J Neuroinflammation, 5:7.
[170] Blasko I, Marx F, Steiner E, Hartmann T, Grubeck- Loebenstein B (1999). TNF alpha plus IFN gamma induce the production of Alzheimer beta-amyloid peptides, and decrease the secretion of APPs. FASEB J, 13:63-68.
[171] Jones G, Strugnell SA, DeLuca HF (1998). Current understanding of the molecular actions of vitamin D. Physiol Rev, 78:1193-1231.
[172] Revelli A, Massobrio M, Tesarik J (1998). Nongenomic effects of 1 alpha, 25-dihydroxyvitamin D3. Trends Endocrinol Metab, 9:419-427.
[173] 173. Wrzosek M, Łukaszkiewicz J, Wrzosek M, Jakubczyk A, Matsumoto H, Piątkiewicz P,et al. (2013).Vitamin D and the central nervous system. Pharmacol Rep, 65:271-278.
[174] Eyles DW, Burne TH, McGrath JJ (2013).Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol, 34:47-64.
[175] Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D (2002). New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab, 13:100-105.
[176] Gezen-Ak D, Dursun E, Ertan T, Hanağasi H, Gürvit H, Emre M,et al. (2007). Association between vitamin D receptor gene polymorphism and Alzheimer's disease. Tohoku J Exp Med, 12:275-282.
[177] Wang L, Hara K, Van Baaren JM, Price JC, Beecham GW, Gallins PJ,et al. (2012).Vitamin D receptor and Alzheimer's disease: a genetic and functional study. Neurobiol Aging, 33:1844.e1-9.
[178] Gezen-Ak D, Dursun E, Bilgiç B, Hanağasi H, Ertan T, Gürvit H,et al. (2012). Vitamin D receptor gene haplotype is associated with late-onset Alzheimer's disease. Tohoku J Exp Med, 228:189-196.
[179] Annweiler C, Llewellyn DJ, Beauchet O (2013). Low serum vitamin D concentrations in Alzheimer's disease: a systematic review and meta-analysis. J Alzheimers Dis, 33:659-674.
[180] Zhao Y, Sun Y, Ji HF, Shen L (2013). Vitamin D levels in Alzheimer's and Parkinson's diseases: a meta-analysis. Nutrition, 29:828-832.
[181] Afzal S, Bojesen SE, Nordestgaard BG (2014). Reduced 25-hydroxyvitamin D and risk of Alzheimer's disease and vascular dementia. Alzheimers Dement, 10:296-302.
[182] Hooshmand B, Lokk J, Solomon A, Mangialasche F, Miralbell J, Spulber G,et al. (2014). Vitamin D in relation to cognitive impairment, cerebrospinal fluid biomarkers, and brain volumes. J Gerontol A Biol Sci Med Sci, doi: 10.1093/gerona/glu022 [Epub ahead of print].
[183] Dursun E, Gezen-Ak D, Yilmazer S (2011). A novel perspective for Alzheimer's disease: vitamin D receptor suppression by amyloid-β and preventing the amyloid-β induced alterations by vitamin D in cortical neurons. J Alzheimers Dis, 23:207-219.
[184] Sutherland MK, Somerville MJ, Yoong LK, Bergeron C, Haussler MR, McLachlan DR (1992). Reduction of vitamin D hormone receptor mRNA levels in Alzheimer as compared to Huntington hippocampus: correlation with calbindin-28k mRNA levels. Brain Res Mol Brain Res, 13:239-250.
[185] Ito S, Ohtsuki S, Nezu Y, Koitabashi Y, Murata S, Terasaki T (2011). 1 alpha, 25-dihydroxyvitamin D3 enhances cerebral clearance of human amyloid-β peptide (1-40) from mouse brain across the blood-brain barrier. Fluids Barriers CNS, 8:20.
[186] Masoumi A, Goldenson B, Ghirmai S, Avagyan H, Zaghi J, Abel K,et al. (2009). 1 alpha, 25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimer's disease patients. J Alzheimers Dis, 17:703-717.
[187] Yu J, Gattoni-Celli M, Zhu H, Bhat NR, Sambamurti K, Gattoni-Celli S,et al. (2011).Vitamin D3-enriched diet correlates with a decrease of amyloid plaques in the brain of AβPP transgenic mice. J Alzheimers Dis, 25:295-307.
[188] Jiang T, Yu JT, Tan L (2012). Novel disease-modifying therapies for Alzheimer's disease. J Alzheimers Dis, 31: 475-492.
[189] Townsend M (2011). When will Alzheimer's disease be cured? A pharmaceutical perspective. J Alzheimers Dis, 24 Suppl 2:43-52.
[1] Yiqin Wang,Rong Zhou,Jianliu Wang. Relationship between Hypothyroidism and Endometrial Cancer[J]. Aging and disease, 2019, 10(1): 190-196.
[2] Szkup Malgorzata, Brodowski Jacek, Aleksander Jerzy Owczarek, Choręza Piotr, Jurczak Anna, Grochans Elzbieta. Searching for Factors Raising the Incidence of Metabolic Syndrome Among 45-60-Year-Old Women[J]. Aging and disease, 2018, 9(5): 831-842.
[3] Lourenco Joana, Serrano Antonio, Santos-Silva Alice, Gomes Marcos, Afonso Claudia, Freitas Paula, Paul Constanca, Costa Elisio. Cardiovascular Risk Factors Are Correlated with Low Cognitive Function among Older Adults Across Europe Based on The SHARE Database[J]. Aging and disease, 2018, 9(1): 90-101.
[4] Zou Jing, Chen Zhigang, Liang Caiqian, Fu Yongmei, Wei Xiaobo, Lu Jianjun, Pan Mengqiu, Guo Yue, Liao Xinxue, Xie Huifang, Wu Duobin, Li Min, Liang Lihui, Wang Penghua, Wang Qing. Trefoil Factor 3, Cholinesterase and Homocysteine: Potential Predictors for Parkinson’s Disease Dementia and Vascular Parkinsonism Dementia in Advanced Stage[J]. Aging and disease, 2018, 9(1): 51-65.
[5] Cao Yiwei, Wang Rui-Hong. Associations among Metabolism, Circadian Rhythm and Age-Associated Diseases[J]. Aging and disease, 2017, 8(3): 314-333.
[6] Fu Xin, Wang QiuHong, Wang ZhiBin, Kuang HaiXue, Jiang Pinghui. Danggui-Shaoyao-San: New Hope for Alzheimer's Disease[J]. Aging and disease, 2016, 7(4): 502-513.
[7] Mariolis Anargiros, Foscolou Alexandra, Tyrovolas Stefanos, Piscopo Suzanne, Valacchi Giuseppe, Tsakountakis Nikos, Zeimbekis Akis, Bountziouka Vassiliki, Gotsis Efthimios, Metallinos George, Tyrovola Dimitra, Tur Josep-Antoni, Matalas Antonia-Leda, Lionis Christos, Polychronopoulos Evangelos, Panagiotakos Demosthenes, for the MEDIS study group. Successful Aging among Elders Living in the Mani Continental Region vs. Insular Areas of the Mediterranean: the MEDIS Study[J]. Aging and disease, 2016, 7(3): 285-294.
[8] Chakrabarti Sasanka, Mohanakumar Kochupurackal P.. Aging and Neurodegeneration: A Tangle of Models and Mechanisms[J]. Aging and disease, 2016, 7(2): 111-113.
[9] R. Dolbow David, S. Gorgey Ashraf. Effects of Use and Disuse on Non-paralyzed and Paralyzed Skeletal Muscles[J]. Aging and disease, 2016, 7(1): 68-80.
[10] Patrícia Fernanda Schuck,Fernanda Malgarin,José Henrique Cararo,Fabiola Cardoso,Emilio Luiz Streck,Gustavo Costa Ferreira. Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations[J]. A&D, 2015, 6(5): 390-399.
[11] A. Fisher Justin, A. McNelis Meredith, S. Gorgey Ashraf, R. Dolbow David, L. Goetz Lance. Does Upper Extremity Training Influence Body Composition after Spinal Cord Injury?[J]. Aging and disease, 2015, 6(4): 271-281.
[12] Bonomini Francesca, Rodella Luigi Fabrizio, Rezzani Rita. Metabolic Syndrome, Aging and Involvement of Oxidative Stress[J]. Aging and disease, 2015, 6(2): 109-120.
[13] Arellanes-Licea Elvira,Caldelas Ivette,De Ita-Pérez Dalia,Díaz-Muñoz* Mauricio. The Circadian Timing System: A Recent Addition in the Physiological Mechanisms Underlying Pathological and Aging Processes[J]. Aging and Disease, 2014, 5(6): 406-418.
[14] Tetsuro Hida,Atsushi Harada,Shiro Imagama,Naoki Ishiguro. Managing Sarcopenia and Its Related-Fractures to Improve Quality of Life in Geriatric Populations[J]. Aging and Disease, 2014, 5(4): 226-237.
[15] Riikka Heikkinen,Tarja Malm,Janne Heikkilä,Anu Muona,Heikki Tanila,Milla Koistinaho,Jari Koistinaho. Susceptibility to Focal and Global Brain Ischemia of Alzheimer Mice Displaying Aβ Deposits: Effect of Immunoglobulin[J]. Aging and Disease, 2014, 5(2): 76-87.
Full text



Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail:
Powered by Beijing Magtech Co. Ltd