Neuropharmacology

Biography

Biography: Ai-Ling Lin

Abstract

Apolipoprotein E ε4 allele (APOE4) is strongest genetic risk facot for late-onset Alzheimer's disease (AD). Brain vascular and metabolic deficits can occur in cognitively normal APOE4 carriers decades before the onset of AD. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of AD-like symptoms in pre-symptomatic APOE4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that APOE4 mice treated with rapamycin had restored cerebral blood flow, blood-brain barrier integrity and glucose metabolism, compared to age- and gender-matched wild-type controls. The preserved vasculature and metabolism were associated with amelioration of incipient learning deficits. We also found that rapamycin restored the levels of the proinflammatory cyclophilin A in vasculature, which may contribute to the preservation of cerebrovascular function in the APOE4 transgenics. Our results show that rapamycin improves functional outcomes in this mouse model and may have potential as an effective intervention to block progression of vascular, metabolic and early cognitive deficits in human APOE4 carriers. As rapamycin is FDA-approved and neuroimaging is readily used in humans, the results of the present study may provide the basis for future AD intervention studies in human subjects.