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Sex differences in Alzheimer's disease: metabolic reprogramming and therapeutic intervention
Journal
Trends in Endocrinology & Metabolism
Volume
32
Number
12
Pages / Article-Number
963-979
Mesh terms
Alzheimer Disease, metabolism; Energy Metabolism; Female; Humans; Male; Menopause; Sex Characteristics
Abstract
Studies on the sporadic form of Alzheimer's disease (AD) have revealed three classes of risk factor: age, genetics, and sex. These risk factors point to a metabolic dysregulation as the origin of AD. Adaptive alterations in cerebral metabolism are the rationale for the Metabolic Reprogramming (MR) Theory of the origin of AD. The theory contends that the progression toward AD involves three adaptive events: a hypermetabolic phase, a prolonged prodromal phase, and a metabolic collapse. This article exploits the MR Theory to elucidate the effect of hormonal changes on the origin and progression of AD in women. The theory invokes bioenergetic signatures of the menopausal transition to propose sexspecific diagnostic program and therapeutic strategies.
