POSSIBLE ROLES OF TRANSGLUTAMINASES IN ALZHEIMERS-DISEASE

The localizations of two transglutaminases [factor XIIIa and tissue tr ansglutaminase (tTG)] and their mRNAs were examined in human brain tis sues from neurologically normal and Alzheimer disease (AD) cases, usin g immunohistochemical and in situ hybridization methods. In all cases, meningeal macrophages and ependymal macrophage/microglia were positiv e for factor XIIIa. The mRNA encoding factor XIIIa was detected in mac rophages and microglia. As reported previously, intense staining with the antibody to factor XIIIa of a subset of microglia was seen in the parietal cortex in AD brains. Few or no microglia were found associate d with classical senile plaques. In contrast, many labeled microglia w ere associated with primitive plaques. Furthermore, most of these cell s were mainly seen in the subpial cortical layer but were very rare in the hippocampus. On the other hand, few factor-XIIIa-positive microgl ia were found in the parietal cortices from non-neurological cases, bu t moderate numbers were found in their hippocampal tissues. TG and its mRNA were localized in astrocytes in all the cases. In AD? a few neur ofibrillary tangles were positive to tTG. These results suggest that t he subsets of microglia which express factor XIIIa may play some roles in the early phase of,AD pathology.