Beta-secretase-cleaved amyloid precursor protein in Alzheimer brain: a morphologic study.
beta-amyloid (Abeta) is the main constituent of senile plaques seen in Alzheimer's disease. Abeta is derived from the amyloid precursor protein (APP) via proteolytic cleavage by proteases beta- and gamma-secretase. In this study, we examined content and localization of beta-secretase-cleaved APP (beta-sAPP) in brain tissue sections from the frontal, temporal and occipital lobe. Strong granular beta-sAPP staining was found throughout the gray matter of all three areas, while white matter staining was considerably weaker. beta-sAPP was found to be localized in astrocytes and in axons. We found the beta-sAPP immunostaining to be stronger and more extensive in gray matter in Alzheimer disease (AD) cases than controls. The axonal beta-sAPP staining was patchy and unevenly distributed for the AD cases, indicating impaired axonal transport. beta-sAPP was also found surrounding senile plaques and cerebral blood vessels. The results presented here show altered beta-sAPP staining in the AD brain, suggestive of abnormal processing and transport of APP.
Sennvik
Kristina
K
Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, KFC Novum, Huddinge, S-141 86, Sweden.
Bogdanovic
N
N
Volkmann
Inga
I
Fastbom
J
J
Benedikz
E
E
D000544:Alzheimer Disease / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D010450:Endopeptidases; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence
D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human