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Aging and disease    2018, Vol. 9 Issue (3) : 334-345     DOI: 10.14336/AD.2017.0809
Orginal Article |
Anserine/Carnosine Supplementation Preserves Blood Flow in the Prefrontal Brain of Elderly People Carrying APOE e4
Ding Qiong1, Tanigawa Kitora1, Kaneko Jun1, Totsuka Mamoru2, Katakura Yoshinori3, Imabayashi Etsuko4, Matsuda Hiroshi4, Hisatsune Tatsuhiro1,*
1Department of Integrated Biosciences, Graduate School of Frontier Sciences, and
2Department of Applied Biochemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan
3Graduate School of Systems Life Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
4Integrative Brain Imaging Center (IBIC), National Center of Neurology and Psychiatry, Tokyo, Japan
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In a previously reported double-blind, randomized controlled trial (RCT), we demonstrated that daily supplementation with anserine (750 mg) and carnosine (250 mg) improves brain blood flow and memory function in elderly people. Here, we conducted a sub-analysis of MRI data and test scores from the same RCT to determine whether anserine/carnosine supplementation specifically benefits elderly people carrying the APOE e4 allele, which is a risk gene for accelerated brain aging and for the onset of Alzheimer’s Disease. We collected data from 68 participants aged 65 years or older who received anserine/carnosine supplementation (ACS) or placebo for 12 months. Subjects were assessed at the start and end of the trial using several neuropsychological tests, including the Wechsler Memory Scale-Logical Memory (WMS-LM). We also collected two types of MRI data, arterial spin labeling (ASL) and diffusion tensor imaging (DTI) at the start and end of the trial. We found that ACS significantly preserved verbal memory (WMS-LM, F[1,65] = 4.2003, p = 0.0445) and blood flow at frontal areas of the brain (FWEcluster level, p < 0.001). Sub-analysis based on the APOE4 genotype showed a significant preservation of blood flow (p = 0.002, by ASL analysis) and white-matter microstructure (p = 0.003, by DTI analysis) at prefrontal areas in APOE4+ subjects in the active group, while there was no significant difference between APOE4- subjects in the active and placebo groups. The effect of ACS in preserving brain structure and function in elderly people carrying APOE4 should be verified by further studies.

Keywords Alzheimer’s Disease      ASL      DTI      verbal memory      RCT      APOE e4     
Corresponding Authors: Hisatsune Tatsuhiro   
About author:

These authors contributed equally to this work.

Issue Date: 05 June 2018
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Ding Qiong
Tanigawa Kitora
Kaneko Jun
Totsuka Mamoru
Katakura Yoshinori
Imabayashi Etsuko
Matsuda Hiroshi
Hisatsune Tatsuhiro
Cite this article:   
Ding Qiong,Tanigawa Kitora,Kaneko Jun, et al. Anserine/Carnosine Supplementation Preserves Blood Flow in the Prefrontal Brain of Elderly People Carrying APOE e4[J]. Aging and disease, 2018, 9(3): 334-345.
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Figure 1.  Longitudinal changes in WMS-LM2 scores. A box plot of the WMS-LM2 data in Table 2 for subjects in the active (n = 30) and placebo (n = 37) groups. Each black dot indicates the difference between the first and final test scores for one volunteer. Box shows the 25-75 percentile, and solid bar shows the median. (One subject in the active group could not complete the final WMS-LM2 test.)
Active groupPlacebo groupp value
Age71.3 (4.8)71.8 (4.8)0.70
Gender (M/F)14/1715/220.61
BMI22.1 (2.1)21.9 (2.3)0.67
Education, years14.7 (2.0)14.3 (3.1)0.52
APOE4+ / APOE4-8/234/330.09
Table 1  Characteristics of participants in a 12-month RCT of ACS.
Figure 2.  Longitudinal changes in WMS-LM2 scores at the mid-term test. A box plot of the change of WMS-LM2 story A data (the score of 6-month test - the score of the initial test) in the active and placebo groups. Each black dot indicates the difference between the first and final test scores for one volunteer. Box shows the 25-75 percentile, and solid bar shows the median.
APOE4+ groupAPOE4- group

Table 2  Subjects grouped by APOE genotype.
Figure 3.  Longitudinal changes in brain perfusion. Brain blood flow was analyzed by ASL. Color indicates regions where changes in brain perfusion differed between the two groups (n = 31 active, 37 placebo). After repeated two-way ANOVA in SPM, the biggest difference was at (x, y, z) = (3, -1, -10) in Montreal Neurological Institute (MNI) coordinate, T=4.09; other two locations were (x, y, z) = (-30, 11, -37) and (24, 11, -43). SPM statistics showed significance between Active and Placebo (Active > Placebo). P(FWE-corr) < 0.001, KE=2857 voxels. Note that the brain locations of the preservation of blood flow by ACS included both sides of temporal lobes, orbitofrontal cortices, dorsolateral prefrontal cortices and anterior cingulate cortices.
FoodActive Group Ave.±SEMPlacebo Group Ave.±SEMp value
AnserinePoultry (656mg/80g)120.9±17.6132.6±17.20.37
(mg/day)Pork (18.4mg/80g)5.1±0.74.9±0.60.66
Beef (43mg/80g)6.2±1.26.4±1.30.79
Red meat Fish (304mg/80g)77.1±10.971.6±8.90.5
Blue back Fish (5.6mg/80g)1.6±0.21.6±0.20.9
White Fish (2.3mg/80g)130.0±23.4145.1±25.20.39
Eel (0mg/80g)0±00±0N.D.
CarnosinePoultry (184mg/80g)33.9±4.937.2±4.80.37
(mg/day)Pork (246mg/80g)68.8±9.565.7±7.90.66
Beef (209mg/80g)30.0±6.031.1±6.10.79
Red meat Fish (24mg/80g)6.1±0.95.6±0.70.5
Blue back Fish (152mg/80g)43.5±5.944.0±5.20.9
White Fish (0mg/80g)0±00±0N.D.
Eel (336mg/80g)7.3±0.87.6±0.70.65
Table 3  Anserine/carnosine intake from the dieta
Figure 4.  ACS preserves blood flow in the prefrontal brain of elderly people. Location of differential longitudinal changes in brain perfusion (red) in the active and placebo groups, on a brain montage from the SPM platform based on equivalent calculations to those in Fig. 3. In the active group, blood flow in these areas was elevated in the follow-up MRI scan.
Figure 5.  Longitudinal changes in brain perfusion in APOE4+ subjects, assessed by ASL. Color indicates brain regions with differences in longitudinal changes in brain perfusion between the active (n = 8) and placebo (n = 4) groups. After repeated two-way ANOVA in SPM, the biggest difference was at (x, y, z) = (-3, 44, -16), T=9.03. SPM statistics showed significance between Active and Placebo (Active > Placebo). P(FWE-corr) = 0.002, KE=378 voxels.
Figure 6.  Longitudinal changes in FA (fraction anisotropy) values in APOE4+ subjects, assessed by DTI. Color indicates areas of the brain where FA values differed between the active (n = 8) and placebo (n = 4) groups. After repeated two-way ANOVA in SPM, the biggest difference was at (x, y, z) = (-32, 32, -4), T=5.75; other two locations were (x, y, z) = (-38, 44, 8) and (-50, 36, 18). SPM statistics showed significance between Active and Placebo (Active > Placebo). P(FWE-corr) = 0.003, KE=754 voxels.
1st testFollow-upChange

ActivePlaceboActivePlaceboActivePlacebop value
WMS-LM-1a13.3 (3.9)15.0 (3.7)14.3 (3.9)14.3 (4.4)0.93 (2.8)-0.65 (3.6)0.054
WMS-LM-2a12.6 (4.0)14.3 (3.9)13.3 (3.9)13.5 (4.4)0.73 (2.9)-0.84 (3.3)0.044*
MMSEb27.5 (1.7)27.6 (1.9)28.2 (2.4)28.5 (1.7)0.74 (2.0)0.92 (1.9)0.53
ADASb9.3 (5.5)8.2 (4.2)7.9 (4.6)6.8 (4.4)-1.4 (3.5)-1.4 (3.3)0.92
SF-36 PCSb48.0 (7.7)49.1 (6.6)45.8 (10.2)48.1 (5.8)-2.2 (7.5)-1.0 (6.1)0.45
SF-36 MCSb54.3 (4.7)52.8 (5.8)56.8 (6.9)a52.4 (7.0)2.3 (7.0)-0.4 (7.4)0.13
BDIb8.2 (6.7)6.8 (4.3)8.0 (6.2)7.2 (5.8)-0.1 (3.7)0.4 (4.5)0.60
Table 4  Changes in psychological test scores in the active and placebo groups.
Figure 7.  Tract-graph analysis of APOE4/E4 subject (#75) in the active group. Top panel shows a seed ROI (x, y, z) = (-30, 30, -4), Sphere Radius = 3.00 mm. Middle panel: a tract-graph using this spherical seed ROI at the start-up scan (Pre). Bottom panel: a tract-graph using this spherical seed ROI at the follow-up scan (Post). Note the longer tract (green) toward the frontal pole seemed to be stronger at the follow-up scan.
[1] Ritchie K, Lovestone S (2002). The dementias. The Lancet, 360:1759-66.
[2] Lindenberger U (2014). Human cognitive aging: corriger la fortune? Science, 346:572-8.
[3] Cooper JK (2014). Nutrition and the brain: what advice should we give? Neurobiol Aging, (Suppl 2) 35: S79-83.
[4] Rokicki J, Li L, Imabayashi E, Kaneko J, Hisatsune T, Matsuda H (2015). Daily Carnosine and Anserine Supplementation Alters Verbal Episodic Memory and Resting State Network Connectivity in Healthy Elderly Adults. Front Aging Neurosci, 7:219.
[5] Hisatsune T, Kaneko J, Kurashige H, Cao Y, Satsu H, Totsuka M, Katakura Y, Imabayashi E, Matsuda H (2016). Effect of Anserine/Carnosine Supplementation on Verbal Episodic Memory in Elderly People. J Alzheimers Dis, 50:149-59.
[6] Boldyrev AA, Aldini G, Derave W (2013). Physiology and pathology of carnosine. Physiol Rev, 93:1803-1845.
[7] Hipkiss AR (2014). Aging risk factors and Parkinson’s disease: contrasting roles of common dietary constituents. Neurobiol Aging, 35:1469-72.
[8] Yeum K-J, Orioli M, Regazzoni L, Carini M, Rasmussen H, Russell RM, Aldini G (2010). Profiling histidine dipeptides in plasma and urine after ingesting beef, chicken or chicken broth in humans. Amino Acids, 38:847-858.
[9] Kubomura D, Matahira Y, Masui A, Matsuda H (2009). Intestinal Absorption and Blood Clearance of L-Histidine-Related Compounds after Ingestion of Anserine in Humans and Comparison to Anserine-Containing Diets. J Agric Food Chem, 57:1781-1785.
[10] Szcześniak D, Budzen S, Kopec W, Rymaszewska J (2014). Anserine and carnosine supplementation in the elderly: Effects on cognitive functioning and physical capacity. Arch. Gerontol Geriatr, 59:485-490.
[11] Kawano N, Awata S, Ijuin M, Iwamoto K, Ozaki N (2013). Necessity of normative data on the Japanese version of the Wechsler Memory Scale-Revised Logical Memory subtest for old-old people. Geriatr Gerontol Int, 13:726-30.
[12] Liu Y, Zhu X, Feinberg D, Guenther M, Gregori J, Weiner MW, Schuff N (2012). Arterial spin labeling MRI study of age and gender effects on brain perfusion hemodynamics. Magn Reson Med, 68:912-22.
[13] Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM (1997). Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA, 278:1349-56.
[14] Giri M, Zhang M, Lü Y (2016). Genes associated with Alzheimer’s disease: an overview and current status. Clin Interv Aging, 11:665-81.
[15] Tai LM, Thomas R, Marottoli FM, Koster KP, Kanekiyo T, Morris AWJ, Bu G (2016). The role of APOE in cerebrovascular dysfunction. Acta Neuropathol, 131:709-723.
[16] Thambisetty M, Beason-Held L, An Y, Kraut MA, Resnick SM (2010). APOE epsilon4 genotype and longitudinal changes in cerebral blood flow in normal aging. Arch Neurol, 67:93-8.
[17] Gietl AF, Warnock G, Riese F, Kälin AM, Saake A, Gruber E, Leh SE, Unschuld PG, Kuhn FP, Burger C, Mu L, Seifert B, Nitsch RM, Schibli R, Ametamey SM, Buck A, Hock C (2015). Regional cerebral blood flow estimated by early PiB uptake is reduced in mild cognitive impairment and associated with age in an amyloid-dependent manner. Neurobiol Aging, 36:1619-28.
[18] Michels L, Warnock G, Buck A, Macauda G, Leh SE, Kaelin AM, Riese F, Meyer R, O’Gorman R, Hock C, Kollias S, Gietl AF (2016). Arterial spin labeling imaging reveals widespread and Aβ-independent reductions in cerebral blood flow in elderly apolipoprotein epsilon-4 carriers. J Cereb Blood Flow Metab, 36:581-95.
[19] Sato Y, Chin Y, Kato T, Tanaka Y, Tozuka Y, Mase M, Ageyama N, Ono F, Terao K, Yoshikawa Y, Hisatsune T (2009). White matter activated glial cells produce BDNF in a stroke model of monkeys. Neurosci Res, 65:71-78.
[20] Cox SR, Ritchie SJ, Dickie DA, Pattie A, Royle NA, Corley J, Aribisala BS, Harris SE, Valdés Hernández M, Gow AJ, Muñoz Maniega S, Starr JM, Bastin ME, Wardlaw JM, Deary IJ (2017). Interaction of APOE e4 and poor glycemic control predicts white matter hyperintensity growth from 73 to 76. Neurobiol Aging, 54:54-58.
[21] Chin Y, Sato Y, Mase M, Kato T, Herculano B, Sekino M, Ohsaki H, Ageyama N, Ono F, Terao K, Yoshikawa Y, Hisatsune T (2010). Transient decrease in cerebral motor pathway fractional anisotropy after focal ischemic stroke in monkey. Neurosci Res, 66:406-411.
[22] Chin Y, Kishi M, Sekino M, Nakajo F, Abe Y, Terazono Y, Ohsaki H, Kato F, Koizumi S, Gachet C, Hisatsune T (2013). Involvement of glial P2Y1 receptors in the cognitive deficits after focal cerebral stroke in a rodent model. J Neuroinflammation, 10:95.
[23] Aoyagi S, Sugino T, Kajimoto Y, Nishitani M (2008a). Safety of long-term administration of CBEX-Dr-containing drink of healthy people. Jpn Pharmacol Ther, 36:213-24.
[24] Aoyagi S, Sugino T, Kajimoto Y, Nishitani M (2008b). Safety of excess administration of CBEX-Dr-containing drink of healthy people. Jpn Pharmacol Ther, 36:225-35.
[25] Kiyohara Y, Shinohara A, Kato I, Shirota T, Kubo M, Tanizaki Y, Fujishima M, Iida M (2003). Dietary factors and development of impaired glucose tolerance and diabetes in a general Japanese population: The Hisayama Study. J Epidemiology, 13:251-258.
[26] Homma A, Fukuzawa K, Tsukada Y, Ishii T, Hasegawa K, Mohs RC (1992). Development of a Japanese version of Alzheimer’s disease Assessment Scale (ADAS). Jpn J Geriatr Psychiatry, 3:647-55.
[27] Uchida K, Shan L, Suzuki H, Tabuse Y, Nishimura Y, Hirokawa Y, Mizukami K, Akatsu H, Meno K, Asada T (2015). Amyloid-β sequester proteins as blood-based biomarkers of cognitive decline. Alzheimers Dement: Diagnosis Assessment Disease Monitoring, 1:270-80.
[28] Beck AT, Steer RA, Brown GK (1996). Manual for the Beck Depression Inventory, 2nd Ed., Pearson, Texas.
[29] Kojima M, Furukawa TA (2003). Japanese manual of the Beck Depression Inventory, 2nd ed., Nihon Bunka Kagakusha, Tokyo.
[30] Ware JE, Sherbourne CD (1992). The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care, 30:474-83.
[31] Lu Y, Nyunt MS, Gwee X, Feng L, Feng L, Kua EH, Kumar R, Ng TP (2012). Life event stress and chronic obstructive pulmonary disease (COPD): associations with mental well-being and quality of life in a population-based study. BMJ Open, 2: e001674.
[32] Yang YG, Kim JY, Park SJ, Kim SW, Jeon OH, Kim DS (2007). Apolipoprotein E genotyping by multiplex tetra-primer amplification refractory mutation system PCR in single reaction tube. J Biotechnol, 131:106-10.
[33] Matsuda H (2013). Voxel-based morphometry of brain MRI in normal aging and Alzheimer’s Disease. Aging Dis, 4:29-37.
[34] Ashburner J (2007). A fast-diffeomorphic image registration algorithm. Neuroimage, 38: 95-113.
[35] Wang R, Benner T, Sorensen AG, Wedeen VJ (2007). Diffusion toolkit: a software package for diffusion imaging data processing and tractography. Proc Intl Soc Mag Reson Med, 15: 3720
[36] Andersson JL, Sotiropoulos SN (2016). An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging. Neuroimage. 125:1063-78.
[37] Smith SM (2002). Fast robust automated brain extraction. Hum Brain Mapp, 17:143-55.
[38] Daiello LA, Gongvatana A, Dunsiger S, Cohen RA, Ott BR; Alzheimer’s Disease Neuroimaging Initiative. (2015). Association of fish oil supplement use with preservation of brain volume and cognitive function. Alzheimers Dement, 11:226-35.
[39] Yassine HN, Braskie MN, Mack WJ, Castor KJ, Fonteh AN, Schneider LS, Harrington MG, Chui HC (2017). Association of Docosahexaenoic Acid Supplementation with Alzheimer Disease Stage in Apolipoprotein E ε4 Carriers: A Review. JAMA Neurol, 74:339-347.
[40] Herculano B, Tamura M, Ohba A., Shimatani M, Kutsuna N, Hisatsune T (2013). β-alanyl-L-histidine rescues cognitive deficits caused by feeding a high fat diet in a transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis, 33:983-997.
[41] Bell RD, Winkler EA, Singh I, Sagare AP, Deane R, Wu Z, Holtzman DM, Betsholtz C, Armulik A, Sallstrom J, Berk BC, Zlokovic BV (2012). Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature, 485:512-6.
[42] Halliday MR, Rege SV, Ma Q, Zhao Z, Miller CA, Winkler EA, Zlokovic BV (2016). Accelerated pericyte degeneration and blood-brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer’s disease. J Cereb Blood Flow Metab, 36:216-227.
[43] Hipkiss AR (2017). On the Relationship between Energy Metabolism, Proteostasis, Aging and Parkinson’s Disease: Possible Causative Role of Methylglyoxal and Alleviative Potential of Carnosine. Aging Dis, 8:334-345.
[44] Hamanaka H, Katoh-Fukui Y, Suzuki K, Kobayashi M, Suzuki R, Motegi Y, Nakahara Y, Takeshita A, Kawai M, Ishiguro K, Yokoyama M, Fujita SC (2000). Altered cholesterol metabolism in human apolipoprotein E4 knock-in mice. Hum Mol Genet, 9:353-61.
[45] Jankowsky JL, Slunt HH, Ratoviski T, Jenkins NA, Copeland NG, Borchelt DR (2001). Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomolecular Engineering, 17:157-165.
[46] Fujishima M, Kawaguchi A, Maikusa N, Kuwano R, Iwatsubo T, Matsuda H (2017). Sample Size Estimation for Alzheimer’s Disease Trials from Japanese ADNI Serial Magnetic Resonance Imaging. J Alzheimers Dis, 56:75-88.
[47] Rajah MN, Wallace LMK, Ankudowich E, Yu EH, Swierkot A, Patel R, Chakravarty MM, Naumova D, Pruessner J, Joober R, Gauthier S, Pasvanis S (2017). Family history and APOE4 risk for Alzheimer’s disease impact the neural correlates of episodic memory by early midlife. Neuroimage Clin, 14:760-774.
[48] KljajevicV, MeyerP, HolzmannC, DyrbaM, KasperE, BokdeAL, FellgiebelA, MeindlT, HampelH, TeipelS; EDSD study group (2014). The ε4 genotype of apolipoprotein E and white matter integrity in Alzheimer’s disease. Alzheimers Dement, 10:401-4.
[49] Adluru N, Destiche DJ, Lu SY, Doran ST, Birdsill AC, Melah KE, Okonkwo OC, Alexander AL, Dowling NM, Johnson SC, Sager MA, Bendlin BB (2014). White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer’s disease. Neuroimage Clin, 4:730-42.
[50] Racine AM, Adluru N, Alexander AL, Christian BT, Okonkwo OC, Oh J, Cleary CA, Birdsill A, Hillmer AT, Murali D, Barnhart TE, Gallagher CL, Carlsson CM, Rowley HA, Dowling NM, Asthana S, Sager MA, Bendlin BB, Johnson SC (2014). Associations between white matter microstructure and amyloid burden in preclinical Alzheimer’s disease: A multimodal imaging investigation. Neuroimage Clin, 4:604-14.
[51] Reinvang I, Espeseth T, Westlye LT (2013). APOE-related biomarker profiles in non-pathological aging and early phases of Alzheimer’s disease. Neurosci Biobehav Rev, 37:1322-35.
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