A ROLE FOR EXTRACELLULAR-MATRIX DEGRADATION AND MATRIX METALLOPROTEINASES IN SENILE DEMENTIA

In brain as in cartilage, the extracellular matrix contains aggregates formed by hyaluronic acid (HA) and proteoglycans. In osteoarthritic c artilage, release of the proteoglycans from the aggregates by cleavage of the HA-binding region results in the accumulation of the HA-bindin g region and in the fragmentation of the released proteoglycans. Strom elysin, a matrix neutral metalloproteinase, is one of the enzymes resp onsible for the cleavage of the HA-binding region. We suggest that a s imilar process also occurs in senile dementia. The brain proteoglycan contains sequences identical to those of aggrecan, which are recognize d and cleaved by stromelysin, and is, in fact, susceptible to stromely sin digestion. Monoclonal antibodies reacting with glial HA-binding pr otein, but not with the parent protein, stained several senile plaques as defined by their reactivity with antibodies to the amyloid-beta pr otein in double-labeling experiments.