Altered NEP2 expression and activity in mild cognitive impairment and Alzheimer's disease.
Neprilysin-2 (NEP2), a close homolog of neprilysin (NEP), degrades amyloid-β (Aβ) and serves an important role in clearing Aβ in vivo. We measured NEP2 and NEP mRNA levels from non-impaired (NI), mild cognitive impaired (MCI), and clinical Alzheimer's disease (AD) subjects in the mid-temporal gyrus, mid-frontal gyrus, caudate, and cerebellum. NEP2 activity levels were also determined. Our results indicate that NEP2 and NEP mRNA expression is altered in MCI subjects relative to NI subjects in AD-susceptible regions. NEP2 enzymatic activity was lowered in association with MCI and AD and was positively associated with cognitive function, independent of diagnostic category. Our finding that NEP2 expression and activity are altered in MCI is significant as these changes may potentially serve as preclinical markers for AD and reduced NEP2 activity may be associated with the development of AD.
Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
Jeffrey Y
JY
Huang
Daniel M
DM
Hafez
Bryan D
BD
James
David A
DA
Bennett
Robert A
RA
Marr
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000704:Analysis of Variance; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002461:Cell Line, Transformed; D060825:Cognitive Dysfunction / Q000378:metabolism / Q000473:pathology*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016014:Linear Models; D008297:Male; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012737:Sex Factors; D014162:Transfection
D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; C436550:MMEL1 protein, human; D015260:Neprilysin