beta-Amyloid protein precursor in Microcebus murinus: genotyping and brain localization.
Senile plaques characterized by beta-amyloid protein (A beta) 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 protein (APP) gene have been directly involved in a few cases of familial AD with early onset (before 60 years). Previous studies have shown that Microcebus murinus, a nonhuman primate, also develops analogous deposits of A beta in the cortical parenchyma and blood vessel walls in the brain. Sequence analysis of exons 16 and 17 of the APP gene, encoding 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 microcebus with or without amyloid deposits revealed that neither the presence of mutations involved in some cases of early onset familial AD nor the presence of a mutational founder effect can explain the amyloidosis observed in some old microcebus of our breeding. Localization of the APP was performed by immunocytochemistry in the brains of adult microcebus (1 to 11 years of age) using two antibodies raised against the C-terminus and N-terminus portions of APP. Microscopic examinations revealed that in the microcebus the APP distribution was similar to that observed in the human: (1) A beta and its precursor were simultaneously observed in amyloid plaques (AP) of the cortical parenchyma; (2) APP was localized in cell bodies and proximal dendrites of neurons, in astrocytes and oligodendrocytes, and in blood vessel and capillary walls; (3) labeling of APP in these structures was correlated with the presence of AP; and (4) labeling of APP increased with the age of the animal.
Silhol
S
S
Ecole Pratique des Hautes Etudes, UMII, Montpellier, France.
Calenda
A
A
Jallageas
V
V
Mestre-Frances
N
N
Bellis
M
M
Bons
N
N
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001808:Blood Vessels / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016565:Cheirogaleidae / Q000378:metabolism*; D014644:Genetic Variation; D005838:Genotype; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D014018:Tissue Distribution
D016564:Amyloid beta-Protein Precursor