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Variation in tau isoform expression in different brain regions and disease states

Majounie, Elisa, Cross, William, Newsway, Victoria, Dillman, Allissa, Vandrovcova, Jana, Morris, Christopher M., Nalls, Michael A., Ferrucci, Luigi, Owen, Michael John, O'Donovan, Michael Conlon, Cookson, Mark R., Singleton, Andrew B., de Silva, Rohan and Morris, Huw R. 2013. Variation in tau isoform expression in different brain regions and disease states. Neurobiology of Aging 34 (7) , 1922.e7-1922.e12. 10.1016/j.neurobiolaging.2013.01.017

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Abstract

Progressive supranuclear palsy (PSP) is the most common atypical parkinsonian disorder. Abnormal tau inclusions, in selected regions of the brain, are a hallmark of the disease and the H1 haplotype of MAPT, the gene encoding tau, is the major risk factor in PSP. A 3-repeat and 4-repeat (4R) tau isoform ratio imbalance has been strongly implicated as a cause of disease. Thus, understanding tau isoform regional expression in disease and pathology-free states is crucial to elucidating the mechanisms involved in PSP and other tauopathies. We used a tau isoform-specific fluorescent assay to investigate relative 4R-tau expression in 6 different brain regions in PSP cases and healthy control samples. We identified a marked difference in 4R-tau relative expression, across brain regions and between MAPT haplotypes. Highest 4R-tau expression levels were identified in the globus pallidus compared with pons, cerebellum, and frontal cortex. 4R-tau expression levels were related to the MAPT H1 and H1c haplotypes. Similar regional variation was seen in PSP case and in control samples.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Uncontrolled Keywords: Progressive supranuclear palsy; Tauopathies; MAPT
Publisher: Elsevier
ISSN: 0197-4580
Last Modified: 10 Oct 2017 16:29
URI: http://orca.cf.ac.uk/id/eprint/75530

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