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Journal of Histochemistry and Cytochemistry, Vol. 48, 1627-1638, December 2000, Copyright © 2000, The Histochemical Society, Inc.

ARTICLE

Novel Method to Quantify Neuropil Threads in Brains from Elders With or Without Cognitive Impairment

Thomas W. Mitchella,b, Jonathan Nissanovc, Li-Ying Hanb, Elliott J. Mufsond, Julie A. Schneiderd, Elizabeth J. Cochrand, David A. Bennettd, Virginia M.-Y. Leea, John Q. Trojanowskia, and Steven E. Arnoldb
a Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
b Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
c School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania
d Rush Alzheimer's Disease Center, Rush–Presbyterian St Luke's Medical Center, Chicago, Illinois

Correspondence to: Steven E. Arnold, Center for Neurobiology and Behavior, U. of Pennsylvania School of Medicine, 142 Clinical Research Bldg., 415 Curie Boulevard, Philadelphia, PA 19104. E-mail: alveus@mail.med.upenn.edu

Pathological alterations in dendrites and axons (i.e., neuritic pathologies) occur in the normal aging brain as well as in brains from elders with mild cognitive impairment and neurodegenerative dementia. These alterations may correlate with clinical measures of cognitive abilities, but the contribution of neuropil threads (NTs), which constitute 85–90% of cortical tau pathology, has not been clear because of the lack of quantitative methodologies. We combined quantitative fractionation and image analysis to devise a strategy for measuring the burden of tau-rich NTs in the entorhinal and perirhinal cortex of brains from elders with and without cognitive impairment, including dementia due to Alzheimer's disease (AD). On the basis of data presented here using this novel strategy, we conclude that this quantitative imaging technique will facilitate efforts to determine the behavioral correlations of neuritic lesions in AD and other brain disorders.

(J Histochem Cytochem 48:1627–1637, 2000)

Key Words: Alzheimer's disease, neurodegenerative disease, stereology, entorhinal cortex, neuropil threads, neurofibrillary tangles, tau, image analysis


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