Alzheimer's Disease

Disease / Phenomenon

Alzheimer's disease is the most common cause of dementia, a progressive neurodegenerative disorder that slowly erodes memory, language, reasoning, and eventually the ability to carry out daily life. It usually begins in the entorhinal cortex and hippocampus, regions central to forming new memories, which is why short-term recall typically falters first while older memories and practiced skills persist longer. Over years the pathology spreads through association cortices, bringing disorientation, word-finding difficulty, impaired judgment, mood and personality change, and loss of independence. Age is the strongest risk factor; genetics contribute substantially, with APOE4 the best-established common risk allele, alongside vascular health, head injury, hearing loss, sleep quality, and metabolic status.

Two protein abnormalities define the disease histologically: extracellular plaques of aggregated amyloid-beta, generated by sequential cleavage of amyloid precursor protein, and intracellular neurofibrillary tangles of hyperphosphorylated tau. Around them sit processes now considered equally central — sustained microglial activation and neuroinflammation, oxidative stress, mitochondrial and bioenergetic failure, impaired insulin signaling in brain tissue, synaptic loss, blood-brain barrier compromise, and reduced glymphatic clearance during sleep. This page separates those processes, follows the molecular pathways within each, and lists the biomarkers used to track them.