Altered cell-matrix associated ADAM proteins in Alzheimer disease

✍ Scribed by 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

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 416 KB
• Volume: 59
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(20000301)59:5<680::aid-jnr11>3.0.co;2-6

✦ Synopsis

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 neurofibrillary alterations. This increase in both ADAM-1 and 2 in cases of Alzheimer disease was verified by immunoblot analysis (P Ͻ 0.05). An ADAMinduced 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.