Altered cell-matrix associated ADAM proteins in Alzheimer disease

Alterations in cell-matrix 'contact' are often related to a disruption of c ell cycle regulation and, as such, occur variously in neoplasia, Given the recent findings showing cell cycle alterations in Alzheimer disease, we und ertook a study of ADAM-1 and 2 (A Disintegrin And Metalloprotease), develop mentally-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 i n association with age-related neurofibrillary alterations. This increase i n both ADAM-1 and 2 in cases of Alzheimer disease was verified by immunoblo t analysis (P < 0.05). An ADAM-induced loss of matrix integration would eff ectively "reset" the mitotic clock and thereby stimulate re-entry into the cell cycle in neurons in Alzheimer disease. Furthermore, given the importan ce of integrins in maintaining short-term memory, alterations in ADAM prote ins or their proteolytic activity could also play a proximal role in the cl inico-pathological manifestations of Alzheimer disease. J, Neurosci, Res. 5 9: 680-684, 2000, (C) 2000 Wiley-Liss, Inc.