Neuroinflammatory mechanisms linking high-fat diets to Alzheimer's disease vulnerability: Beyond the amyloid hypothesis.

ABSTRACT: As global life expectancy increases, Alzheimer's disease (AD) incidence is rising rapidly. While research has long focused on amyloid beta (Aβ) and tau pathology, recent controversies and limited clinical success of Aβ-targeting therapies have challenged their centrality in AD. Emerging evidence highlights neuroinflammation as an earlier and potentially more critical driver of disease, particularly in response to environmental and lifestyle factors. High saturated fat diets (HFD) are strongly associated with increased AD risk in both clinical and preclinical studies. This review examines how HFD promotes AD vulnerability via neuroinflammatory mechanisms, including toll-like receptor 4 activation and complement system overactivation, which contribute to synaptic loss and cognitive decline-o

SUBMITTER: Mackey-Alfonso SE 

PROVIDER: S-EPMC12627239 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature