BETA-A4 PEPTIDE AND CEREBRAL AMYLOID IN A LZHEIMERS-DISEASE

Deposition of large quantities of amyloid substance in the walls of th e cerebral vessels and in the core of the senile plaques is characteri stic of Alzheimer's disease. beta A4 peptide, the main component of th e amyloid substance, is a product of a larger amyloid precursor protei n which has the structure of a transmembrane receptor and is widely di stributed throughout the body. The pathway leading to beta A4 is not y et fully established but could involve lysosomal degradation. It has b een suggested that the beta A4 peptide is of neuronal or vascular orig in. 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 m of the cerebral cortex. These diffus e deposits are devoid of degenerating neurites (i.e. containing abnorm ally 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 t o the density of the classical senile plaques but not to the density o f the diffuse deposits. Although a mutation of the gene coding for the beta A4 peptide appears to be sufficient to induce (or accelerate) Al zheimer's disease, this is undoubtedly an exceptional mechanism. Certa in 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 p laques and of the neurones (which are strongly correlated with clinica l dementia), remain hypothetical.