[Physiopathological bases of Alzheimer disease]

Alzheimer's disease is characterized by the presence of two types of brain lesions: senile plaques and neurofibrillary degeneration. A peptide named beta A4 is the major component of the amyloid substance that constitutes senile plaques. beta A4 is part of a much larger membrane-associated protein known as the amyloid protein precursor (APP) whose gene is on chromosome 21. Mutations on APP gene have been linked to several early-onset AD families, demonstrating the pathogenicity of APP. The amyloid substance, likely neurotoxic, provokes a cascade of biochemical dysfunctions that leads to neurofibrillary degeneration (NFD). NFD is characterized by an intraneuronal filamentous accumulation of abnormally phosphorylated Tau proteins and is followed by cell death. NFD probably first affects the hippocampal region and spreads later to the entire isocortex, progressively provoking an intellectual impairment. Together, these observations show that experimentally-induced lesions in animal or cell models, already at our disposal, will open diagnostic and therapeutical perspectives.