Affiliations: [a] Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA | [b] Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA
Correspondence:
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Correspondence to: Robert A. Marr, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA. Tel.: +1 847 578 8541; Fax: +1 847 578 8515; E-mail: Robert.Marr@rosalindfranklin.edu.
Abstract: 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.
Keywords: Alzheimer's disease, amyloid-β peptide, biomarker, human brain, neprilysin, neprilysin-2
