Altered NEP2 Expression and Activity in Mild Cognitive Impairment and Alzheimer's Disease

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 level of 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.

Distinctive RNA Expression Profiles in Blood Associated With Alzheimer Disease After Accounting for White Matter Hyperintensities

“…The levels of the Aβ-degrading enzyme neprilysin are reduced in human dementia pugilistica cases. Though MME/neprilysin is high in blood in this and other studies, levels of NEP and NEP2 have been reported to be lower, higher or unchanged in AD brain 17 . Notably, Neprilysin protects against cerebral amyloid angiopathy and Aβ-induced degeneration of cerebrovascular smooth muscle cells 18 .…”

Targeting amyloid clearance in Alzheimer's disease as a therapeutic strategy

“…NEP2 shows a different subcellular localization from NEP (Whyteside & Turner, ) and does appear to have a significant contribution to Aβ metabolism in vivo, at least from transgenic studies in AD mouse models (Marr & Hafez, ). Furthermore, NEP2 activity levels are reduced in mild cognitively impaired individuals and AD patients relative to nonimpaired subjects in AD‐susceptible brain regions (Huang, Hafez, James, Bennett, & Marr, ). NEP2 may even prove to be a more selective therapeutic target for up‐regulation of Aβ clearance than NEP itself since it has a more restricted substrate specificity (Whyteside & Turner, ).…”

The activity of blood serum cholinesterases and neprilysin as potential biomarkers of mild-cognitive impairment and Alzheimer’s disease

“…мента в теменной и фронтальной коре головного мозга у аналогичных групп пациентов [22]. Согласно полученным данным, основная холинэсте-разная активность крови обусловлена наличием в плазме БХЭ, поскольку уровень общей активности этого фермен-та на 1-2 порядка выше, чем АХЭ (см.…”

“…В ранее опубликованных исследованиях было по-казано, что содержание НЕП и его мРНК у больных БА являются достоверно более низкими, чем у пациентов контрольной группы соответствующего возраста [21]. Данные литературы также свидетельствуют о том, что со-держание мРНК НЕП и активность его гомолога НЕП2 снижается в средневисочной и среднелобной извилинах, хвостатом ядре и мозжечке головного мозга пациентов с синдромом мягкого когнитивного снижения амнестиче-ского типа (а-MКC) и БА [22]. Дефицит активности НЕП в коре и гиппокампе также наблюдается у животных с на-рушенными когнитивными функциями [16,[23][24][25][26][27].…”