Immunohistochemical and in situ analysis of amyloid precursor-like protein-1 and amyloid precursor-like protein-2 expression in Alzheimer disease and aged control brains

Abstract

Amyloid precursor protein (APP) is a ubiquitously expressed membrane spanning glycoprotein which is endoproteolytically processed to Aβ, a 39–43 amino acid peptide that is the main component of senile plaques in Alzheimer Disease (AD). APP is a member of a highly conserved gene family, including Amyloid Precursor-Like Proteins (APLPs) APLP1 and APLP2. We now characterize APLP1 and APLP2 mRNA and protein expression in AD and aged control brains. Using in situ hybridization in hippocampal tissue from control and AD brain, we show that APLP1 and APLP2 mRNA are expressed primarily in the granule cells of the dentate gyrus, in areas CA1–CA3, and subiculum. Immunohistochemistry reveals staining for both APLP1 and APLP2 in neurons and blood vessels in AD and control cases. In addition, in AD brain, large dystrophic neurites in a subset of senile plaques are conspicuously labeled with APLP1 and APLP2 antibodies. The aged control brains have significantly fewer immunoreactive plaques and dystrophic neurites. The regional, cellular, and subcellular distribution of APLP1 and APLP2 overlap with each other and with APP. These observations support the hypothesis that the members of this family of proteins may perform similar functions.