Differential cerebral deposition of IDE and NEP in sporadic and familial Alzheimer's disease

Verónica Berta Dorfman, Laura Pasquini, Miguel Riudavets, Juan José López-Costa, Andrés Villegas, Juan Carlos Troncoso, Francisco Lopera, Eduardo Miguel Castaño, Laura Morelli

Research output: Contribution to journalArticle

Abstract

Alzheimer's disease (AD) is characterized by amyloid β (Aβ) accumulation in the brain and is classified as familial early-onset (FAD) or sporadic late-onset (SAD). Evidences suggest that deficits in the brain expression of insulin degrading enzyme (IDE) and neprilysin (NEP), both proteases involved in amyloid degradation, may promote Aβ deposition in SAD. We studied by immunohistochemistry IDE and NEP cortical expression in SAD and FAD samples carrying the E280A presenilin-1 missense mutation. We showed that IDE, a soluble peptidase, is linked with aggregated Aβ40 isoform while NEP, a membrane-bound protease, negatively correlates with amyloid angiopathy and its expression in the senile plaques is independent of aggregated amyloid and restricted to SAD cases. NEP, but not IDE, is over-expressed in dystrophic neurites, both proteases are immunoreactive in activated astrocytes but not in microglia and IDE was the only one detected in astrocytes of white matter from FAD cases. Collectively, our results support the notion that gross conformational changes involved in the modification from " natively folded-active" to " aggregated-inactive" IDE and NEP may be a relevant pathogenic mechanism in SAD.

Original languageEnglish (US)
Pages (from-to)1743-1757
Number of pages15
JournalNeurobiology of Aging
Volume31
Issue number10
DOIs
StatePublished - Oct 1 2010

    Fingerprint

Keywords

  • Alzheimer's disease
  • Amyloid β
  • Astrocytes
  • Human brain
  • Insulin degrading enzyme
  • Neprilysin
  • Presenilin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Dorfman, V. B., Pasquini, L., Riudavets, M., López-Costa, J. J., Villegas, A., Troncoso, J. C., Lopera, F., Castaño, E. M., & Morelli, L. (2010). Differential cerebral deposition of IDE and NEP in sporadic and familial Alzheimer's disease. Neurobiology of Aging, 31(10), 1743-1757. https://doi.org/10.1016/j.neurobiolaging.2008.09.016