The association between small vessel infarcts and the activities of amyloid-β peptide degrading proteases in apolipoprotein E4 allele carriers.
Small vessel (SV) and large vessel (LV) brain infarcts are distinct pathologies. Using a homebound elderly sample, the numbers of either infarct subtypes were similar between those apolipoprotein E4 allele (ApoE4) carriers (n = 80) and noncarriers (n = 243). We found that the higher the number of SV infarcts, but not LV infarcts, a participant had, the higher the activity of substrate V degradation in serum especially among ApoE4 carriers (β = +0.154, SE = 0.031, P < .0001) after adjusting for the confounders. Since substrate V degradation could be mediated by insulin-degrading enzyme (IDE) or/and angiotensin-converting enzyme (ACE), but no relationship was found between SV infarcts and specific ACE activities, blood IDE may be a useful biomarker to distinguish the brain infarct subtypes. Insulin-degrading enzyme in blood may also imply an important biomarker and a pathological event in Alzheimer disease through SV infarcts in the presence of ApoE4.
1Department of Pharmacology & Experimental Therapeutics, Boston University Medical Campus, Boston, MA, USA.
Haihao
H
Zhu
Rafeeque A
RA
Bhadelia
Zhiheng
Z
Liu
Linh
L
Vu
Huajie
H
Li
Tammy
T
Scott
Peter
P
Bergethon
Mkaya
M
Mwamburi
James L
JL
Rosenzweig
Irwine
I
Rosenberg
Wei Qiao
WQ
Qiu
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D020520:Brain Infarction / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D003430:Cross-Sectional Studies; D003704:Dementia / Q000175:diagnosis; D005260:Female; D006579:Heterozygote; D006801:Humans; D007339:Insulysin / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D010447:Peptide Hydrolases / Q000378:metabolism
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D010447:Peptide Hydrolases; D007339:Insulysin