The Molecular Pathophysiology Of Late Onset Alzheimer's Disease

Abstract

Alzheimer's Disease is a progressive degenerative neurological disease that is characterized by the insidious loss of memory, with the degree of cognitive impairment worsening over progressive decades. It has distinct neuropathological findings that define the disease, including, amyloid (Aβ) plaques, neuritic plaques, and neurofibrillary tangles composed of filamentous tau proteins. The accumulation and deposition of Aβ peptide in the brain has been long been suspected to be a primary cause of Alzheimer's disease (AD). Aβ plaques provide the nexus for the formation of neuritic plaques. Microglia interacts with the neuritic plaques, releasing cytokines and reactive species that may be responsible for dysconformation of tau, leading to neurofibrillary tangles (NFTs). Tau pathology, NFTs, and neuronal death are likely the cause of cognitive deterioration in AD. The molecular pathophysiology of AD demonstrates a complex interplay between production and clearance, stimulation and overstimulation. The result is a disease whose cure needs to take multiple different forms, including targeting Aβ accumulation or clearance, immune modulation, tau interaction accumulation.