Alzheimer's disease — Amyloid-beta

GSK-3 beta inhibition would reduce tau hyperphosphorylation and slow decline in mild-to-moderate Alzheimer's.

CSF p-tau181 dropped by 28% but ADAS-Cog showed no difference from placebo; the high-dose arm was halted for safety.

Why it matched: shares MAPT/tau · similar wording · same research area · mechanism: Proteostasis · failed the same way: Target engaged, outcome unchanged

A TREM2 agonist antibody would boost microglial plaque clearance and slow decline in early Alzheimer's.

Microglial activation markers rose and soluble TREM2 in CSF dropped, but CDR-SB scores were unchanged at 12 months.

Why it matched: similar wording · same research area · mechanism: Proteostasis · failed the same way: Target engaged, outcome unchanged

Removing aggregated amyloid beta with aducanumab would slow decline on the Clinical Dementia Rating Sum of Boxes in early Alzheimer's disease.

Both phase 3 trials were halted for futility on pooled interim data. In the fuller analyses, EMERGE met the primary endpoint (−0.39 for high dose vs placebo, P = .012) but ENGAGE did not (+0.03, P = .833), with 3,285 patients across 348 sites.

Why it matched: shares APP/amyloid-beta · same research area · similar wording · mechanism: Proteostasis

Long-term voluntary running would reduce insoluble amyloid, neuroinflammation and non-cognitive behavioural problems in the 5xFAD mouse model of Alzheimer's disease.

After 24 weeks of wheel running started before heavy plaque formation (female mice, n = 30), microglia, cytokines and insoluble amyloid-beta were unchanged. Runners actually developed hindlimb clasping earlier (p = 0.009) and showed more anxiety-like and exploratory behaviour.

Why it matched: shares APP/amyloid-beta · same research area · mechanism: Proteostasis · mechanism: Synaptic & neuronal function

Activating LXR or RXR receptors, which raise APOE and are reported to help clear amyloid beta, would lower amyloid beta 40 in the brain and spinal fluid of rats.

Treating normal rats for 3 or 7 days with the LXR agonist T0901317 or the RXR agonist bexarotene did not significantly change amyloid beta 40 in the brain or spinal fluid.

Why it matched: shares APP/amyloid-beta · same research area · mechanism: Proteostasis