alpha- and beta-secretase: profound changes in Alzheimer's disease.
The amyloid plaque, a neuropathological hallmark of Alzheimer's disease, is produced by the deposition of beta-amyloid (Abeta) peptide, which is cleaved from Amyloid Precursor Protein (APP) by the enzyme beta-secretase. Only small amounts of Abeta form in normal brain; more typically this is precluded by the processing of APP by alpha-secretase. Here, we describe a decrease in alpha-secretase (81% of normal) and a large increase in beta-secretase activity (185%) in sporadic Alzheimer's disease temporal cortex. Since alpha-secretase is present principally in neurons known to be vulnerable in Alzheimer's disease, and there is known competition between alpha- and beta-secretase for the substrate APP, it is significant that the majority of Alzheimer samples tested here were low in alpha-secretase. Eighty percent of Alzheimer brains examined had an increase in beta-secretase, a decrease in alpha-secretase, or both; which may account for the means by which the majority of people develop Alzheimer's disease.
Tyler
Susan J
SJ
Molecular Neurobiology Unit, URCN (Care of the Elderly) University of Bristol, Bristol Royal Infirmary, Bristol, UK.
Dawbarn
David
D
Wilcock
Gordon K
GK
Allen
Shelley J
SJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D013223:Statistics as Topic; D013702:Temporal Lobe / Q000201:enzymology*
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D002795:Choline O-Acetyltransferase; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human