Expression patterns of β‐amyloid precursor protein (β‐APP) in neural and nonneural human tissues from alzheimer's disease and control subjects

Abstract

Both neural and nonneural human tissues from patients with or without Alzheimer's disease (AD) were surveyed to detect the presence of the β‐amyloid protein and its precursors. This was accomplished using polyclonal and monoclonal antibodies to epitopes in the 695 amino acid long β‐APP (i.e., β‐APP 695), as well as in related β‐APPs. Immunoreactivity in β‐APP in brain was prominent in senile plaques, extraneuronal tangles, and neurons. Outside the brain, β‐APP staining was seen in neurons and satellite glial cells of the dorsal root, enteric and trigeminal gangila, the adeno‐and neurohypophysis, megakaryocytes, and adrenal gland in samples from patients with AD and those without AD. Western blots of neocortex revealed three major proteins with apparent molecular masses of 105, 115, and 125 kDa in the insoluble membrane‐associated fractions, while two broad bands with a molecular weight centered at about 100 and 120 kDa were detected in soluble fractions. In addition, the pituitary and adrenal glands as well as cardiac muscle revealed prominent immunobands in membrane‐associated fractions. Notably, other nonneural tissues were devoid of β‐APP immunoreactivity. Thus, the β‐APPs are detectable only in a limited number of nonneural tissues. Taken together, these data suggest that β‐APPs produced in the brain are sources of β‐APP peptides that accumulate as senile plaques in AD.