Localization of beta-secretase memapsin 2 in the brain of Alzheimer's patients and normal aged controls.
Chronic accumulation of beta-amyloid in the brain has been shown to result in complex molecular and cellular changes that accompany neurodegeneration in Alzheimer's disease (AD). In this study, we examined the expression of a newly identified beta-secretase, memapsin 2 (M2) or beta-site APP cleaving enzyme in deparaffinized sections from 10 AD patients and 10 aged matched controls and in frozen samples of parietal cortex from 11 AD and 8 controls. M2 is mainly expressed in neurons, with high levels in CA4 to CA2 regions and transentorhinal cortex and low or intermediate levels in CA1, subiculum, and granule cells of the dentate gyrus. The majority of AD brains showed an increase of M2 expression in the CA1, but a decrease in the transentorhinal cortex. A subset of controls and AD patients had high M2 expression in parietal neocortex. Double-staining revealed that senile plaques are not directly associated with the soma of M2-expressing neurons. Neurofibrillary tangles were associated with lower M2 expression in AD. These data indicate that beta-secretase M2 may not be straightforwardly involved in amyloid plaque formation in AD brain.
Sun
Anyang
A
Department of Anatomy & Neurobiology, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA.
Koelsch
Gerald
G
Tang
Jordan
J
Bing
Guoying
G
D000368:Aged; D000369:Aged, 80 and over; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000096:biosynthesis; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000096:biosynthesis; D016282:Aspartic Acid Endopeptidases / Q000032:analysis / Q000096:biosynthesis*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D010450:Endopeptidases; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D010296:Parietal Lobe / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D053764:Presenilin-1
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human