COLOCALIZATION OF TRUNCATED TAU-FRAGMENTATION AND DNA FRAGMENTATION IN ALZHEIMERS-DISEASE NEURONS

MONOCLONAL antibody MN423 stains all hallmarks of tau neurofibrillary pathology in Alzheimer's disease (AD), without reacting with full-leng th tau. It recognizes tau molecules which are cleaved at Glu-391, sugg esting that tau is endogenously truncated in AD brains. We investigate d whether truncation of tau takes place in pre-tangle neurones. Our re sults showed that tau truncation occurs inside AD neurones in the abse nce of other signs of AD neurofibrillary pathology. Using in situ end labelling (ISEL) of DNA we found evidence for DNA fragmentation in a s ignificant subpopulation of MN423-positive neurones. Our results there fore suggest that tau truncation is an early intracellular event prece ding cell death in AD.