Neurodegenerative Diseases

Disease / Phenomenon

Neurodegenerative diseases are disorders in which specific populations of neurons progressively lose function and die, producing steadily worsening deficits in movement, cognition, or both. The category includes Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, frontotemporal dementia, and multiple system atrophy, among others. Each has a characteristic vulnerable region — hippocampal and cortical neurons in Alzheimer's, dopaminergic cells of the substantia nigra in Parkinson's, motor neurons in ALS — which explains why symptoms differ so markedly despite substantial mechanistic overlap. Onset is typically insidious, with pathology accumulating for years or decades before clinical presentation, and age remains the dominant risk factor across the group.

A shared theme is protein misfolding and aggregation: amyloid-beta and tau, alpha-synuclein, TDP-43, and polyglutamine-expanded huntingtin each form deposits that spread between connected regions in a prion-like manner. Around this sit common failures — impaired proteostasis through the ubiquitin-proteasome system and autophagy, mitochondrial dysfunction and bioenergetic deficit, oxidative stress, disrupted calcium handling, axonal transport failure, glutamate excitotoxicity, and chronic microglial and astrocytic activation sustaining neuroinflammation. Blood-brain barrier changes and impaired glymphatic clearance contribute. This page organizes these processes, traces their molecular pathways, and identifies the biomarkers that make them measurable.