CHOLINERGIC FIBER LOSS ASSOCIATED WITH DIFFUSE PLAQUES IN THE NONDEMENTED ELDERLY - THE PRECLINICAL STAGE OF ALZHEIMERS-DISEASE

Diffuse plaques are the earliest Alzheimer-type lesions in Down's synd rome and are a putative marker for the preclinical stage of Alzheimer' s disease (AD). As a cerebral cortical cholinergic deficit is one of t he characteristics which defines AD, we examined the brains of individ uals who had died without a history of neurological disease to determi ne whether this deficit is present in association with diffuse plaques . Of the 24 cases collected, 14 were older than 60 years of age (mean 69.2 years) and 10 were younger (mean 29.6 years). Of the 14 older cas es, 9 had diffuse plaques in the entorhinal cortex (ECx) and/or inferi or temporal gyrus (ITG). The older cases were divided into two groups (plaque-positive or plaque-negative cases). These groups did not diffe r significantly with respect to age, post-mortem delay, synaptophysin immunoreactivity or neurofibrillary tangle density. Cholinergic fibre densities were estimated in sections stained using acetylcholinesteras e (AChE) enzyme histochemistry. Mean AChE fibre density was decreased in both the ITG and ECx (approximately 30% and 50% depletion, respecti vely) in the plaque-positive group compared to the plaque-negative gro up and in both areas the mean fibre density of the plaque-positive gro up was about 50% of that in the younger group. These results suggest t hat diffuse plaques in the non-demented elderly are associated with an accelerated age-related cortical cholinergic deficit and, therefore r epresent the preclinical stage of AD.