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Journal of Histochemistry and Cytochemistry, Vol. 50, 99-106, January 2002, Copyright © 2002, The Histochemical Society, Inc.

ARTICLE

Improved Detection of Substantia Nigra Pathology in Alzheimer's Disease

Julie A. Schneidera,c, Julia L. Bieniasb, David W. Gilleyb,c, David E. Kvarnberga, Elliott J. Mufsonc, and David A. Bennetta,b,c
a Rush Alzheimer's Disease Center, Rush University and Rush Presbyterian–St. Luke's Medical Center, Chicago, Illinois
b Rush Institute for Healthy Aging, Rush University and Rush Presbyterian–St. Luke's Medical Center, Chicago, Illinois
c Department of Neurological Sciences, Rush University and Rush Presbyterian–St. Luke's Medical Center, Chicago, Illinois

Correspondence to: Julie A. Schneider, 1645 W. Jackson Blvd., Suite 675, Chicago, IL 60612. E-mail: jschneid@rush.edu

The role of substantia nigra pathology in Alzheimer's disease (AD) is uncertain. Detection of pathology may be obscured by intraneuronal neuromelanin and influenced by stains. We determined methods for optimal visualization of nigral pathology in 45 cases of AD. For detection of Lewy bodies (LBs), we compared ubiquitin and {alpha}-synuclein immunostains to hematoxylin and eosin (H&E). For neurofibrillary tangles (NFTs) and neuropil threads (NTs), we compared Gallyas silver and paired helical filament (PHF) immunostains, after bleaching of melanin, to modified Bielschowsky, Gallyas, and PHF alone. The number of LB cases was not different using the three stains. However, more LBs per section were detected using {alpha}-synuclein (z=4.88, p<0.001). Twice the number of cases exhibited NFT (z=8.21; p<0.001) and the mean NFT number per section was 2.8–5.2-fold greater, using Gallyas and PHF after bleaching compared to without bleaching ({chi}2=142.17; p<0.001). More NTs (z=6.54; p<0.001) were observed with PHF and Gallyas after bleaching. With optimal methods, we found LBs in 27%, NFTs in 89%, and NTs in all 45 AD cases. We show that detection of nigra pathology is influenced by histological method. Clinicopathological studies using these methods are needed to determine the role of nigral pathology in AD.

(J Histochem Cytochem 50:99–106, 2002)

Key Words: substantia nigra, neurofibrillary tangles, neuropil threads, Lewy body, Alzheimer's disease, neuromelanin


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