LOCALIZATION OF TISSUE INHIBITOR OF MATRIX METALLOPROTEINASES IN ALZHEIMERS-DISEASE AND NORMAL BRAIN

Based upon the hypothesis that metalloproteinases and their inhibitors might be involved in the pathogenesis of Alzheimer's disease, we stud ied brain samples of eight cases of Alzheimer's disease, six other pat hological entities and three elderly controls for tissue inhibitor of metalloproteinase (TIMP) immunoreactivity. Specificity was supported b y a loss of immunoreactivity following antigen preabsorption of antise ra. Areas studied included ependyma, choroid plexus, frontoparietal, h ippocampal and cerebellar cortex, n. basalis of Meynert, basal ganglia , midbrain, pens, and medulla. TIMP positivity was localized to neurit ic senile plaques, neurofibrillary tangles and Purkinje cells. The pat tern of TIMP plaque staining was similar to that observed with anti ta u and SP18 antibodies. It differed from that observed with anti SP40, HAM 56 and GFAP antibodies. The selective localization of TIMP to the neuritic lesions of Alzheimer's disease in a codistribution with the a myloid precursor protein and abnormally phosphorylated and truncated t au supports a possible role for metalloproteinases and their inhibitor s in the evolution of these lesions.