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

Majounie, Elisa ORCID: https://orcid.org/0000-0003-2800-1091, Cross, William, Newsway, Victoria, Dillman, Allissa, Vandrovcova, Jana, Morris, Christopher M., Nalls, Michael A., Ferrucci, Luigi, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, 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:	28 Oct 2022 09:44
URI:	https://orca.cardiff.ac.uk/id/eprint/75530

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