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Altered NEP2 expression and activity in mild cognitive impairment and Alzheimer's disease

Jeffrey Y Huang1, Daniel M Hafez, Bryan D James

  • 1Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.

Journal of Alzheimer'S Disease : JAD
|October 20, 2011
PubMed

Insights

Neprilysin-2 (NEP2) levels and activity decrease in mild cognitive impairment and Alzheimer's disease, potentially serving as early biomarkers for AD progression.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Genetics

Background:

  • Neprilysin-2 (NEP2), a homolog of neprilysin (NEP), plays a role in degrading amyloid-beta (Aβ).
  • Aβ accumulation is a hallmark of Alzheimer's disease (AD).
  • Understanding NEP2's role in AD pathogenesis is crucial for developing early diagnostic markers.

Purpose of the Study:

  • To investigate alterations in NEP2 and NEP mRNA expression and NEP2 enzymatic activity in non-impaired (NI), mild cognitive impairment (MCI), and clinical Alzheimer's disease (AD) subjects.
  • To determine the association between NEP2 levels/activity and cognitive function.
  • To explore the potential of NEP2 as a preclinical biomarker for AD.

Main Methods:

  • Measurement of NEP2 and NEP mRNA levels in post-mortem brain tissue (mid-temporal gyrus, mid-frontal gyrus, caudate, cerebellum) from NI, MCI, and AD subjects.
  • Determination of NEP2 enzymatic activity levels.
  • Correlation analysis between NEP2/NEP expression, NEP2 activity, and cognitive function.

Main Results:

  • NEP2 and NEP mRNA expression were altered in MCI subjects compared to NI subjects, particularly in AD-susceptible brain regions.
  • NEP2 enzymatic activity was reduced in individuals with MCI and AD.
  • Lowered NEP2 activity was positively associated with cognitive function, irrespective of diagnostic group.

Conclusions:

  • NEP2 expression and activity are significantly altered in the early stages of cognitive decline (MCI).
  • These alterations may serve as preclinical biomarkers for Alzheimer's disease.
  • Reduced NEP2 activity could be linked to the development and progression of AD.

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