Decreases in protease nexins in Alzheimer's disease brain.
A marked and significant reduction of protease nexin-1 (PN-1) and PN-2/amyloid beta protein precursor (A beta PP) was observed in selected regions of Alzheimer's disease (AD) brains as compared to those of aged-matched controls. Correlative analysis indicated a relationship between PN-1 reduction and the severity of pathologic alterations. A statistically significant inverse correlation was noted between the level of PN-1 activity and the density of tau-positive dystrophic neurites in the hippocampus. In view of the ability of thrombin and PN-1 activity to regulate neurite outgrowth, it is possible that abnormal thrombin and PN-1 interactions may play a role in dystrophic neurite formation. The presence of clusters of dystrophic neurites around the capillaries suggests that blood-brain barrier (BBB) dysfunction may enhance such abnormal interactions. The decrease in PN-2/A beta PP levels in AD brains could possibly contribute to neuronal degeneration in AD in view of the ability of PN-2/A beta PP to protect neurons against the toxic effects of the A beta.
Department of Pathology (Neuropathology), University of California, Irvine 92717, USA.
B H
BH
Choi
R C
RC
Kim
P J
PJ
Vaughan
A
A
Lau
W E
WE
Van Nostrand
C W
CW
Cotman
D D
DD
Cunningham
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology; D006801:Humans; D016501:Neurites / Q000201:enzymology / Q000473:pathology; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D012044:Regression Analysis; D058258:Serpin E2; D013917:Thrombin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D058255:Protease Nexins; D011956:Receptors, Cell Surface; C545486:SERPINE2 protein, human; D058258:Serpin E2; D016875:tau Proteins; D013917:Thrombin