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Title
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Common Variant in GRN Is a Genetic Risk Factor for Hippocampal Sclerosis in the Elderly
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Author
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Abstract
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| Background: Hippocampal sclerosis (HpScl) is common in elderly subjects with dementia, either alone or accompanied by other pathologic processes. It is also found in >70% of frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions (FTLD-TDP). TDP-43 inclusions are detected in >20% of Alzheimer disease (AD) and >70% of HpScl cases. The most common cause of FTLD-TDP is mutation in the progranulin gene (GRN). Recently, a common genetic variant in the 3' untranslated region (3' UTR) of GRN (rs5848; c.*78C>T) located in a microRNA binding site regulated progranulin expression, and the T-allele was increased in FTLD-TDP compared to controls. Objective: The goal of this study was to determine if the 3'UTR variant in GRN was associated with TDP-43 immunoreactivity in AD with and without HpScl. Methods: 644 cases of pathologically confirmed AD, including 57 with HpScl, were screened for TDP-43 immunoreactivity and were genotyped at the GRN 3'UTR single-nucleotide polymorphism rs5848 using previously published methods. Results: There was a trend (p = 0.06) for TDP-43 immunoreactivity, but a very significant (p = 0.005) association of HpScl with the variant, with 72% of AD with HpScl carrying a T-allele, compared to 51% of AD without HpScl carrying a T-allele. Conclusion: The results suggest that a genetic variant in GRN leading to decreased levels of progranulin may be a risk factor for HpScl in AD, while its role in TDP-43 immunoreactivity in AD remains less certain. Copyright (C) 2010 S. Karger AG, Basel |
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Language
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English
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Source (journal)
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Neuro-degenerative diseases. - Basel
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Source (book)
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9th International Conference on Alzheimer's and Parkinson's Diseases, (AD/PD), MAR 11-15, 2009, Prague, CZECH REPUBLIC
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Publication
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Basel
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Karger
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2010
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ISSN
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1660-2854
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DOI
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10.1159/000289231
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Volume/pages
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7
:1-3
(2010)
, p. 170-174
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ISI
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000276739200038
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Full text (Publisher's DOI)
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