From: Interpreting Alzheimer’s disease clinical trials in light of the effects on amyloid-β
Selective Aβ42-lowering method | Brain Aβ42 lowering (%) | Observed cognitive or pathological benefits in deficient Tg mouse | Mouse strain | Reference |
---|---|---|---|---|
ICV injection of preaggregated Aβ42/Aβ40 | Aβ42/40 3:7 ratio; 1:9 ratio inactive | Passive avoidance and contextual fear conditioning | Wild type; intraventricular Aβ administration | [44] |
BRI-Aβ40 and BRI-Aβ42 transgenes | 50-400% increased Aβ40 (decreased 42/total ratio) | 60-90% decreased plaque; improved survival; however, these mice exhibited no Aβ-dependent cognitive phenotypes | Tg2576 and Tg-Aβ40 | |
EVP-0015962 | 50% after single 30 mpk dose | Contextual fear conditioning, gliosis 75% plaque load, after 50 weeks at 60 mpk/day | Tg2576 | [49] |
CHF5074 | No significant change (4–9 month treatment) | Contextual memory, 50-75% decreased plaque burden, astrogliosis, synaptophysin levels, neurogenesis | Tg2576 | |
GSM-2 | 0-30% at 0.1-3 mpk, respectively | Y maze improvements at 0.1-3 mpk in mice aged 5.5 months | Tg2576 | [35] |
GSM-2 | 50-60% nascent Aβ 2 hours after 10 mpk | Y maze and plaque pathology in mice aged 10–18 months | Tg2576 | [36] |
JNJ40418677 | 50% max lowering 30 mpk single dose | Up to 96% decreased plaque area and number after 7 months at 120 mpk/day | Tg2576 | [55] |
Compound 4 | 40% decrease 100 mpk single dose | 48-76% decrease of plaque Aβ after 7 months at 50 mpk/day | Tg2576 | [54] |