Accumulation of SNAP-25 immunoreactive material in axons of Alzheimer's disease.

Neurofibrillary tangles and neuropil threads, both made of hyperphosphorylated tau proteins, point to an alteration of microtubules in Alzheimer's disease. The aim of this study was to test the consequences of these lesions on axoplasmic flow, which is dependent on intact microtubule assembly. We assessed the transport of synaptic proteins from the neuronal cell body to axonal terminals, using SNAP-25 (synaptosomal-associated protein of 25 kD) immunohistochemistry as a marker of impaired axonal transport. A sample from the supra-marginalis gyrus was obtained from 29 individuals over 75 years of age whose cognitive function had been prospectively assessed. Accumulation of immunoreactive material in swollen axons was observed in the white matter of severely demented individuals, and their number was correlated with the density of neurofibrillary tangles (r = 0.53, p = 0.005) and of focal Abeta deposits (r = 0.61, p = 0.001). This supports the hypothesis of a dysfunction of the cytoskeleton in Alzheimer's disease. An unexpected finding was the lack of correlation between SNAP-25 immunohistochemistry in the grey matter and the intellectual status or the density of neurofibrillary tangles, focal Abeta deposits and neuronal profiles. These results which question the role of synaptic markers as correlates of dementia, should be extended to other brain areas.