[Alzheimer disease. Role of beta A4 peptide and cerebral amyloid substance].
Deposition of large quantities of amyloid substance in the walls of the cerebral vessels and in the core of the senile plaques is characteristic of Alzheimer's disease. beta A4 peptide, the main component of the amyloid substance, is a product of a larger amyloid precursor protein which has the structure of a transmembrane receptor and is widely distributed throughout the body. The pathway leading to beta A4 is not yet fully established but could involve lysosomal degradation. It has been suggested that the beta A4 peptide is of neuronal or vascular origin. The beta A4 peptide is found in diffuse deposits in the cortex and cerebellum as well as in the basal ganglia before the classic senile plaques appear, mainly in layer III of the cerebral cortex. These diffuse deposits are devoid of degenerating neurites (i.e. containing abnormally phosphorylated tau protein). The classical senile plaques contain numerous degenerating neurites linking them to the connective network of the cortex. The intellectual deficit is correlated significantly to the density of the classical senile plaques but not to the density of the diffuse deposits. Although a mutation of the gene coding for the beta A4 peptide appears to be sufficient to induce (or accelerate) Alzheimer's disease, this is undoubtedly an exceptional mechanism. Certain mutations involving the beta A4 precursor protein gene increase in vitro the production of beta A4. The molecular and morphological steps leading, from the accumulation of the peptide (which in itself has no clinical expression) to the neurofibrillary pathology of the senile plaques and of the neurones (which are strongly correlated with clinical dementia), remain hypothetical.
Duyckaerts
C
C
Laboratoire de Neuropathologie R. Escourolle, Hôpital de la Salpêtrière, Paris.
Delaère
P
P
He
Y
Y
Seilhean
D
D
Hauw
J J
JJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism / Q000503:physiopathology; D006801:Humans
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor
Maladie d'Alzheimer. Rôle du peptide beta A4 et de la substance amyloïde cérébrale.