Three investigators have applied different histopathologic methods (mo
dified Bielschowsky silver methods, Congo red-gallocyanin) to differen
tiate Alzheimer's disease (AD) (n = 7 subjects; four with very mild de
mentia and three with moderate to advanced dementia) neuropathology fr
om brain changes associated with aging in three nondemented individual
s who had been evaluated using a validated dementia severity staging i
nstrument [Washington University clinical Dementia Rating (CDR)] gener
ally within a year of death. The presence of elevated numbers of neoco
rtical (frontal and temporal) diffuse, mature, and total senile plaque
s (SP) was strongly correlated with the presence of clinical AD but di
d not equate with CDR dementia severity. Neocortical neurofibrillary t
angle (NFT) density as well as hippocampal NFT and SP density in this
small series did not differentiate statistically between AD and contro
ls. NFT density appeared to correlate with CDR better than SP density.
Quantitative histopathologic assessment of AD markers in only a few b
rain regions can accurately predict the presence of clinical AD, inclu
ding the very mild form of the disease. This is especially true for SP
in the neocortex.