TDP‐43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease

Annals of Neurology - Tập 61 Số 5 - Trang 435-445 - 2007
Catalina Amador1, Wen‐Lang Lin1, Zeshan Ahmed1, David Personett1, Peter Davies2, Ranjan Duara3,4, Neill R. Graff‐Radford5, Michael Hutton1, Dennis W. Dickson1
1Department of Neuroscience Mayo Clinic College of Medicine, Jacksonville, FL
2Departments of Pathology and Neuroscience, Albert Einstein College of Medicine, Bronx, NY
3Miller School of Medicine, University of Miami, Miami
4Wien Center for Alzheimer's Disease and Memory Disorders, Mt. Sinai Medical Center, Miami Beach
5Department of Neurology Mayo Clinic College of Medicine, Jacksonville, FL

Tóm tắt

AbstractObjectiveThis study aimed to determine the frequency of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD‐U) in the setting of hippocampal sclerosis (HpScl) and Alzheimer's disease (AD) using immunohistochemistry for TAR DNA binding protein 43 (TDP‐43), a putative marker for FTLD‐U.MethodsInitially, 21 cases of HpScl associated with a variety of other pathological processes and 74 cases of AD were screened for FTLD‐U with TDP‐43 immunohistochemistry. A confirmation study was performed on 93 additional AD cases. Specificity of TDP‐43 antibodies was assessed using double‐immunolabeling confocal microscopy, immunoelectron microscopy, and biochemistry.ResultsTDP‐43 immunoreactivity was detected in 71% of HpScl and 23% of AD cases. Double immunostaining of AD cases for TDP‐43 and phospho‐tau showed that the TDP‐43–immunoreactive inclusions were usually distinct from neurofibrillary tangles. At the ultrastructural level, TDP‐43 immunoreactivity in AD was associated with granular and filamentous cytosolic material and only occasionally associated with tau filaments. Western blots of AD cases showed a band that migrated at a higher molecular weight than normal TDP‐43 that was not present in AD cases without TDP‐43 immunoreactivity.InterpretationThese results suggest that as many as 20% of AD cases and more than 70% of HpScl cases have pathology similar to that found in FTLD‐U. Whether this represents concomitant FTLD‐U or is analogous to colocalization of α‐synuclein and tau in AD, reflecting a propensity for codeposition of abnormal protein conformers, remains to be determined. Ann Neurol 2007;61:435–445

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Annals of Neurology

Tập 61 Số 5

435-445

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