ACCUMULATION OF SNAP-25 IMMUNOREACTIVE MATERIAL IN AXONS OF ALZHEIMERS-DISEASE

NEUROFIBRILLARY tangles and neuropil threads, both made of hyperphosph orylated tau proteins, point to an alteration of microtubules in Alzhe imer's disease. The aim of this study was to test the consequences of these lesions on axoplasmic flow, which is dependent on intact microtu bule assembly. We assessed the transport of synaptic proteins from the neuronal cell body to axonal terminals, using SNAP-25 (synaptosomal-a ssociated protein of 25 kD) immunohistochemistry as a marker of impair ed axonal transport. A sample from the supramarginalis gyrus was obtai ned from 29 individuals over 75 years of age whose cognitive function had been prospectively assessed. Accumulation of immunoreactive materi al in swollen axons was observed in the white matter of severely demen ted individuals, and their number was correlated with the density of n eurofibrillary tangles (r = 0.53, p = 0.005) and of focal A beta depos its (r = 0.61, p = 0.001). This supports the hypothesis of a dysfuncti on of the cytoskeleton in Alzheimer's disease. An unexpected finding w as the lack of correlation between SNAP-25 immunohistochemistry in the grey matter and the intellectual status or the density of neurofibril lary tangles, focal A beta deposits and neuronal profiles. These resul ts which question the role of synaptic markers as correlates of dement ia, should be extended to other brain areas.