title: Variation in tau isoform expression in different brain regions and disease states.
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.
authors: MRC Centre for Neuropsychatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK.
authors: Elisa
authors: E
authors: Majounie
authors: William
authors: W
authors: Cross
authors: Victoria
authors: V
authors: Newsway
authors: Allissa
authors: A
authors: Dillman
authors: Jana
authors: J
authors: Vandrovcova
authors: Christopher M
authors: CM
authors: Morris
authors: Michael A
authors: MA
authors: Nalls
authors: Luigi
authors: L
authors: Ferrucci
authors: Michael J
authors: MJ
authors: Owen
authors: Michael C
authors: MC
authors: O'Donovan
authors: Mark R
authors: MR
authors: Cookson
authors: Andrew B
authors: AB
authors: Singleton
authors: Rohan
authors: R
authors: de Silva
authors: Huw R
authors: HR
authors: Morris
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001923:Brain Chemistry / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D005917:Globus Pallidus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D016875:tau Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D020033:Protein Isoforms; D016875:tau Proteins