Signs of Alzheimer's Disease: Tied to Aging.

Alzheimer's disease (AD) is a neurodegenerative disorder closely associated with aging, and its pathogenesis involves the interaction of multidimensional pathophysiologic processes. This review outlines the core mechanisms linking aging and AD. The amyloid cascade hypothesis emphasizes that abnormal deposition of amyloid-β (Aβ) triggers neuronal damage and synaptic dysfunction, which is exacerbated by aging-associated declines in protein clearance. Neuroinflammation, a synergistic pathogenetic factor in AD, is mediated by microglia activation, creating a vicious cycle with Aβ and tau pathology. The cholinergic hypothesis states that the degeneration of cholinergic neurons in the basal forebrain can lead to acetylcholine deficiency, which is directly associated with cognitive decline. Endothelial disorders promote neuroinflammation and metabolic waste accumulation through blood-brain barrier dysfunction and cerebral vascular abnormalities. In addition, glutamate-mediated excitotoxicity and mitochondrial dysfunction (e.g., oxidative stress and energy metabolism imbalance) further lead to neuronal death, and aging-associated declines in mitochondrial autophagy exacerbate such damage. This review also explores the application of animal models that mimic AD and aging in studying these mechanisms and summarizes therapeutic strategies targeting these pathways. Future studies need to integrate multi-targeted therapies and focus on the role of the aging microenvironment in regulating AD pathology in order to develop more effective early diagnosis and treatment options.