Decreased neprilysin immunoreactivity in Alzheimer disease, but not in pathological aging

Deng Shun Wang, Richard B. Lipton, Mindy J. Katz, Peter Davies, Herman Buschke, Gail Kuslansky, Joe Verghese, Steven G. Younkin, Chris Eckman, Dennis W. Dickson

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Although evidence suggests that extensive cortical β-amyloid (Aβ) deposition is essential in Alzheimer disease (AD), it is also detected in nondemented elderly individuals with pathologic aging (PA). Given evidence that neutral endopeptidase (NEP) or neprilysin, a key enzyme for clearance of Aβ, is decreased in AD, the goal of the present study was to determine if NEP was also decreased in PA. We measured NEP immunoreactivity in frontal cortex of 12 AD and six PA cases and compared this with 10 normal (N) elderly individuals. None had any significant other pathology, and they were similar with respect to age, sex, and postmortem delay. In addition, Aβ1-40 and Aβ1-42 were measured by enzyme-linked immunosorbent assay (ELISA), whereas tau, synaptophysin, and α-synuclein were measured on Western blots. The AD cases had more neuritic plaques, neurofibrillary tangles, higher Braak stage, and more tau immunoreactivity in frontal cortex than both PA and N. In contrast, both PA and AD had more senile plaques and Aβ1-42 than N. NEP immunoreactivity was decreased in AD but not in PA. The decrease was unlikely the result of neuronal or synaptic loss because NEP immunoreactivity in frontotemporal degeneration with comparable degrees of synaptic loss as the AD cases was not different from control subjects. Although NEP enzyme activity was decreased in approximately half the AD cases, on average, it was not decreased compared with N or PA. The results add further evidence that PA is distinct from AD and indicate that decreased Aβ degradation by NEP is unlikely to contribute significantly to amyloid deposition in PA or, in many cases, of AD.

Original languageEnglish (US)
Pages (from-to)378-385
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Issue number5
StatePublished - May 2005


  • Alzheimer disease
  • Amyloid
  • Neprilysin
  • Neurofibrillary tangles
  • Pathological aging
  • Senile plaques
  • Synaptic markers
  • Tau

ASJC Scopus subject areas

  • General Medicine


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