Alzheimer disease (AD) is characterized by two hallmark pathological features: extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein. The amyloid cascade hypothesis proposes that abnormal processing of amyloid precursor protein (APP) by beta-secretase (BACE1) and gamma-secretase produces Aβ42 peptides that aggregate into oligomers and fibrils. Aβ42 oligomers are the most neurotoxic species, disrupting synaptic function, activating microglia, and triggering tau hyperphosphorylation. Tau, normally a microtubule-stabilizing protein, becomes hyperphosphorylated and detaches from microtubules, forming paired helical filaments that aggregate into NFTs. Tau pathology spreads in a stereotypical pattern (Braak staging): entorhinal cortex → hippocampus → association cortices → primary cortices, correlating with progressive memory loss then broader cognitive decline. Cholinergic neuron loss in the nucleus basalis of Meynert reduces acetylcholine availability, impairing memory consolidation. Neuroinflammation (microglial activation, astrogliosis), synaptic loss, and mitochondrial dysfunction accelerate neurodegeneration. Synaptic density loss is the strongest pathological correlate of cognitive decline.