Rodent Models of Amyloid-Beta Feature of Alzheimer’s Disease: Development and Potential Treatment Implications

Poon Chi Him, Wang Yingyi, Fung Man-Lung, Zhang Chengfei, Lim Lee Wei

Table 1 Mouse models of amyloid-beta pathology in Alzheimer’s disease.

Animal model Model background Transgene Amyloid pathology Other pathology Behavioral test Ref. Tg2576 C57BL/6 Human APP695 (Swedish) Aβ plaques at 10-12 months,oligomeric Aβ generation Synaptic loss at 15-18 months. Behavioral impairment in novel object recognition at 12-15 months, Morris water maze at 6 months and Y maze at 10 months. [55, 123, 237] TgAPP23 C57BL/6J Human APP751 (Swedish) Aβ plaques at 6 months Increased level of phospho-tau at 6 months, phospho-tau deposition surrounding plaques at 12 months, neuronal loss in area of CA1 at 14-18 months. Behavioral impairment in novel object recognition at 3-4 months, Morris water maze at 3 months. [56, 238, 239] PDAPP Swiss Webster × B6D2F1 Human APP (Indiana) Aβ plaques at 6-9 months Synaptic loss. Behavioral impairment in novel object recognition at 6 months, Morris water maze at 3 months. [54, 240] J20 C57BL/6 × DBA/2 F2 Human APP (Swedish and Indiana) Diffuse amyloid deposits at 5-6 months and larger neuritic plaques at 9 months Phospho-neurofilaments. Behavioral impairment in novel object recognition at 4 months, Morris water maze at 6-9 months. [53, 68, 241, 242] TgCRND8 C3H/He × C57BL/6 Human APP695 (Swedish and Indiana) Aβ plaques at 3 months,dense core plaques at 5 months, spreading to the cerebellum and brainstem by 8-9 months Astrocytic gliosis and microglial activation in regions around plaques. Behavioral impairment in novel object recognition at 3-5 months, Morris water maze at 3 months. [67, 69, 243] AppNL-F C57BL/6 Human APP (Swedish and Iberian) Aβ plaque at 6 months Synaptic loss, microgliosis and astrocytosis Behavioral impairment in Y-maze at 18 months, no impairment in Morris water maze at 18 months [76] 5XFAD Tg6799×Tg7031 ×Tg7092 Human APP (Swedish, Florida, London); Human PS1 (M146L, L286V) Intraneuronal Aβ42 accumulation at 1.5 months, amyloid deposition, gliosis, at 2 months Significant neurodegeneration and neuronal loss. Behavioral impairment in Y-maze at 4-5 months, decreased Interest in social-related behaviors at 3-12 months. Morris water maze at 4 months. [81, 244, 245] APP23 x PS1-R278I C57BL/6J Human APP23 (Swedish K651N, M652L); Human PS1 (R278I) Aβ plaque at 6 months Astrocytosis. Behavioral impairment in Y-maze at 3-4 months; no significant impairment in Morris water maze [82] TREM2-BAC x 5XFAD TREM2-BAC: FVB/NJ; 5XFAD: C57BL/6X SJL Human APP (Swedish, Florida, London); Human PS1 (M146L, L286V) less cortical amyloid plaque at 7 months compared to 5XFAD mice Enhanced process ramification and phagocytic marker expression in plaque-associated microglia; improved dystrophic neurites. No cognitive impairment in contextual fear conditioning test. [85] 3xTg-AD C57BL6/129SvJ Human APP (Swedish); Human PS1 (M146V); Human Tau (P301L) Aβ plaque at 6 months synaptic dysfunction and increased microglia activation at 6 months; Tau alteration at 12-15 months Retention deficits in Morris water maze and contextual fear memory [87-89]