- Progressive β-amyloid plaque development in cortex, hippocampus and subiculum from an age of 6 months onwards
- Pyroglutamate-modified Aβ42 (Aβ3(pE)-42) is detected in the insoluble brain fraction from 7 months onwards
- Progressive microgliosis and astrocytosis from an age of 6 months
- Cognitive impairment in the Morris water maze paradigm from an age 5 months and hippocampal LTP deficit at 8 months (not tested earlier)
- CAA pathology and micro-bleedings from 8 and 12-15 months of age, respectively
Progressive total plaque load (an anti-Aβ antibody) and dense plaque load (Thioflavin S) in the subiculum as measured by IHC (mean ± SEM, N = 10).
Data from a study (Easton et al., 2013) that showed a significant improvement in reference memory in APPxPS1 mice along with a dose-dependent reduction in brain Aβ. These results suggest that donepezil may alleviate cognitive impairments in Alzheimer’s disease, in part, by reducing brain Aβ.
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- Original paper: Dewachter et al., 2000: Aging Increased Amyloid Peptide and Caused Amyloid Plaques in Brain of Old APP/V717I Transgenic Mice by a Different Mechanism than Mutant Presenilin1. DOI: 10.1523/JNEUROSCI.20-17-06452.2000
Therapeutic intervention papers:
- Easton et al., 2013: Effects of sub-chronic donepezil on brain Abeta and cognition in a mouse model of Alzheimer’s disease. DOI: 10.1007/s00213-013-3152-3
- Hansen et al., 2016: Long-Term Treatment with Liraglutide, a Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist, Has No Effect on β-Amyloid Plaque Load in Two Transgenic APP/PS1 Mouse Models of Alzheimer’s Disease. DOI: https://pubmed.ncbi.nlm.nih.gov/27421117/
- Latta-Mahieu et al., 2017: Systemic immune-checkpoint blockade with anti-PD1 antibodies does not alter cerebral amyloid-b burden in several amyloid transgenic mouse models. DOI: 10.1002/glia.23260