Altered cell-matrix associated ADAM proteins in Alzheimer disease

Jennifer L. Gerst, Arun K. Raina, Ibrahim Pirim, Andrew McShea, Peggy L.R. Harris, Sandra L. Siedlak, Atsushi Takeda, Robert B. Petersen, Mark A. Smith

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Alterations in cell-matrix 'contact' are often related to a disruption of cell cycle regulation and, as such, occur variously in neoplasia. Given the recent findings showing cell cycle alterations in Alzheimer disease, we undertook a study of ADAM-1 and 2 (A Disintegrin And Metalloprotease), developmentally-regulated, integrin-binding, membrane-bound metalloproteases. Our results show that whereas ADAM-1 and 2 are found in susceptible hippocampal neurons in Alzheimer disease, these proteins were not generally increased in similar neuronal populations in younger or age-matched controls except in association with age-related neurofibriliary alterations. This increase in both ADAM-1 and 2 in cases of Alzheimer disease was verified by immunoblot analysis (P < 0.05). An ADAM-induced loss of matrix integration would effectively 'reset' the mitotic clock and thereby stimulate re-entry into the cell cycle in neurons in Alzheimer disease. Furthermore, given the importance of integrins in maintaining short-term memory, alterations in ADAM proteins or their proteolytic activity could also play a proximal role in the clinico-pathological manifestations of Alzheimer disease. (C) 2000 Wiley- Liss, Inc.

Original languageEnglish
Pages (from-to)680-684
Number of pages5
JournalJournal of Neuroscience Research
Volume59
Issue number5
DOIs
Publication statusPublished - 2000
Externally publishedYes

Keywords

  • ADAM-1
  • ADAM-2
  • Alzheimer disease
  • Mitosis
  • Neoplasia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Altered cell-matrix associated ADAM proteins in Alzheimer disease'. Together they form a unique fingerprint.

Cite this