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Characterization of TDP43 protein in primary progressive aphasia (PPA) and frontotemporal dementia (FTD) with Alzheimer disease (AD) pathology
Author(s) -
Bigio Eileen H,
Mishra Manjari,
Johnson Nancy,
Mao Henry,
Mesulam Marsel
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a21-c
Subject(s) - frontotemporal lobar degeneration , pathology , frontotemporal dementia , corticobasal degeneration , semantic dementia , dementia , immunohistochemistry , pick's disease , hippocampus , ubiquitin , medicine , disease , psychology , chemistry , neuroscience , biochemistry , gene
The purpose of this study was to determine whether autopsied cases of PPA or FTD with AD pathology have concomitant frontotemporal degeneration with ubiquitin (Ub) inclusions (FTLD‐U), since AD pathology, also ubiquitin positive, can mask FTLD‐U pathology. Ub positive intranuclear inclusions (NIIs), when present, can signify FTLD‐U in cases with AD, but most FTLD‐U cases do not have NIIs. A recent report shows that FTLD‐U inclusions are labeled by antibodies to TDP43 protein, and that TDP43 does not label the tangles (NFTs) or plaques (NPs) of AD. At Northwestern, we have brain autopsies from 25 PPA and 32 FTD subjects. Of these 57, 23 have NFTs and NPs in the density and distribution classifiable by most neuropathologists as AD, one with Ub positive NIIs. 31 have FTLD: 21 have FTLD‐U and 10 have tauopathies (5 corticobasal degeneration, 2 Pick disease, and 3 non‐classifiable). The three others have vascular dementia, adult polyglucosan body disease, and dementia lacking distinctive histology. We performed TDP43 immunohistochemistry on sections of frontal and temporal lobe and hippocampus from these 57 brain autopsies. TDP43 labeled all cases of FTLD‐U, and labeled more FTLD‐U pathology in the AD case with Ub positive NIIs than could be appreciated with ubiquitin. Other AD cases did not have TDP43 positive pathology. We conclude that, in our series, FTLD‐U is rarely combined with pathologic AD in clinical FTD. Supported in part by AG13854