Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer's disease
L. M. Bierer, P. R. Hof, D. P. Purohit, L. Carlin, J. Schmeidler, K. L. Davis and D. P. Perl
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY.
OBJECTIVE: To determine the relationships between dementia severity and the
extent of histopathologic lesions in a variety of brain regions.
Neocortical and hippocampal ratings for neurofibrillary tangles (NFTs) and
senile plaques (SPs) were compared in 70 cases of clinically and
neuropathologically confirmed Alzheimer's disease. DESIGN: Neuropathologic
case series. Dementia severity was assessed by postmortem chart review with
use of the extended Clinical Dementia Rating Scale (CDR). Linear
association between CDR scores and NFT and SP scores were assessed by
partial correlation, controlling for age at death. SETTING: Studies were
conducted at the Alzheimer's Disease Research Center of the Mount Sinai
Medical Center, New York, NY. MAIN OUTCOME MEASURE: Association between CDR
scores and neuropathologic changes assessed with the Consortium to
Establish a Registry for Alzheimer's Disease semiquantitative scale.
RESULTS: Among these lesion scores, only NFTs showed a significant
association with CDR score, and only for neocortical regions. In
particular, NFT densities in the superior temporal cortex were most
strongly correlated with dementia severity, followed by those in the
inferior parietal and midfrontal cortex. No such correlations were apparent
for the amygdala, hippocampus, or entorhinal cortex. Medial temporal lobe
structures displayed high NFT scores, even in cases of mild dementia.
Senile plaques did not correlate significantly with CDR score in any
region. CONCLUSIONS: These data support the notion that neocortical
neuronal degeneration, as indicated by NFT formation, is a critical
determinant of the clinical progression of Alzheimer's disease and suggest
that medial temporal lobe structures may represent the initial site of NFT
formation. While SP density correlates with age at death, there is no
correlation between SP counts and dementia severity. These results further
suggest that the clinical presentation of dementia may be closely related
to neurodegeneration in neocortical regions within the temporal lobe.
