Imipramine binds to amyloid-β and extends the survival of Alzheimer's disease patients

Imipramine directly binds amyloid-β monomers, inhibits apoE–amyloid-β interaction, and is linked to reduced 10-year all-cause mortality in AD patients.

• Why it matters: The study addresses how apoE contributes to AD pathology and whether targeting apoE–amyloid-β can translate into better clinical outcomes, including survival.
• What they did: They used nuclear magnetic resonance spectroscopy to characterize imipramine–amyloid-β binding, tested effects in hiPSC-derived AD cerebral organoids and imipramine-treated transgenic AD rats, and analyzed AD patient mortality in the National Alzheimer's Coordinating Center database with Kaplan-Meier and Cox models.
• The result: Imipramine reduced amyloid-β accumulation and neuronal cell loss in AD organoids and improved female rat reference memory and hippocampal cellularity; in patients, imipramine prescriptions were associated with lower all-cause mortality over 10 years versus other TCAs, non-TCAs, or no antidepressants.

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