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(American Journal of Pathology. 2001;158:1481-1490.)
© 2001 American Society for Investigative Pathology

Regular Articles

Structural Analysis of Pick’s Disease-Derived and in Vitro-Assembled Tau Filaments

Michelle E. King^*, Nupur Ghoshal^*, Joseph S. Wall, Lester I. Binder^* and Hanna Ksiezak-Reding

From the Department of Cell and Molecular Biology and The Cognitive Neurology and Alzheimer’s Disease Center,^*
Northwestern University Medical School, Chicago, Illinois; the Biology Department,
Brookhaven National Laboratory, Upton, New York; and the Department of Pathology,
Albert Einstein College of Medicine, Bronx, New York

Pick’s and Alzheimer’s diseases are distinct neurodegenerative disorders both characterized in part by the presence of intracellular filamentous tau protein inclusions. The tight bundles of paired helical filaments (PHFs) of tau protein found in Alzheimer’s disease (AD) differ from the tau filaments of Pick’s disease in their morphology, distribution, and pathological structure as identified by silver impregnation. The filaments of Pick’s disease are loosely arranged in pathognomonic spherical inclusions found in ballooned neurons, whereas the tau pathology of AD is classically described as a triad of neuropil threads, neurofibrillary tangles, and dystrophic neurites surrounding and invading plaques. In this study we used the high-resolution technique of scanning transmission electron microscopy to characterize and compare the filaments found in Pick’s disease with those found in AD. In addition, we determined the mass/nm length and density of arachidonic acid-induced in vitro-assembled filaments. Three morphologically distinct populations of Pick’s filaments were identified but each was indistinguishable from AD-PHFs in mass/nm length and density. Filaments assembled in vitro from single isoforms were similar in mass/nm length, but less dense than AD-PHFs and Pick’s disease filaments. Finally, we provide clear structural evidence that a PHF, whether found in disease or assembled in vitro, is composed of two distinct intertwined filaments.

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