New biochemical insights to unravel the pathogenesis of Alzheimer's lesions.
Purification of amyloid plaque core proteins (APCP) from Alzheimer's disease brains to complete homogeneity and in high yield permitted its chemical fractionation and characterization of its components. APCP is mainly made of beta-amyloid (beta A) and an assortment of glycoproteins (accounting for 20%) rich in carbohydrates compatible with N- and O-linked saccharides. When added to tissue culture of sympathetic and sensory neurons APCP and beta A inhibited neuritic sprouting, a reversible phenomenon at low doses. Higher concentrations of both substances kill the neurons in culture. APCP is significantly more toxic than beta A, suggesting the minor components may play an important role in increasing the toxicity of beta A. If the observed toxic effects of APCP in situ are occurring in vivo during the course of AD, then the accumulation of these extracellular proteins could be largely responsible for some of the neuronal death observed in this neuropathology.
Roher
A E
AE
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Palmer
K C
KC
Capodilupo
J
J
Wakade
A R
AR
Ball
M J
MJ
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D006801:Humans
D016564:Amyloid beta-Protein Precursor