BETA-AMYLOID PROTEIN-PRECURSOR IN MICROCEBUS-MURINUS - GENOTYPING ANDBRAIN LOCALIZATION

Senile plaques characterized by P-amyloid protein (AP) deposits around dystrophic neurites and glial cells are more abundant in the cerebral cortical parenchyma of Alzheimer's disease (AD) patients than in the aged population. Four different mutations in the amyloid precursor pro tein (APP) gene have been directly involved in a few cases of familial AD with early onset (before 60 years). Previous studies have shown th at Microcebus murinus, a nonhuman primate, also develops analogous dep osits of A beta in the cortical parenchyma and blood vessel walls in t he brain. Sequence analysis of exons 16 and 17 of the APP gene, encodi ng for A beta, revealed that even if nucleotide divergences occurred, the resulting peptide is completely homologous with the human A beta. The systematic comparison of the A beta nucleotide sequence in microce bes with or without amyloid deposits revealed that neither the presenc e of mutations involved in some cases of early onset familial AD nor t he presence of a mutational founder effect can explain the amyloidosis observed in some old microcebes of our breeding. Localization of the APP was performed by immunocytochemistry in the brains of adult microc ebes (1 to 11 years of age) using two antibodies raised against the C- terminus and N-terminus portions of APP. Microscopic examinations reve aled that in the microcebe the APP distribution was similar to that ob served in the human: (1) A beta and its precursor were simultaneously observed in amyloid plaques (AP) of the cortical parenchyma; (2) APP w as localized in cell bodies and proximal dendrites of neurons, in astr ocytes and oligodendrocytes, and in blood vessel and capillary walls; (3) labeling of APP in these structures was correlated with the presen ce of AP; and (4) labeling of APP increased with the age of the animal . (C) 1996 Academic Press, Inc.