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

• Published in: Neurobiology of aging Vol. 34; no. 7; pp. 1922.e7 - 1922.e12
• Main Authors: Majounie, Elisa, Cross, William, Newsway, Victoria, Dillman, Allissa, Vandrovcova, Jana, Morris, Christopher M, Nalls, Michael A, Ferrucci, Luigi, Owen, Michael J, O'Donovan, Michael C, Cookson, Mark R, Singleton, Andrew B, de Silva, Rohan, Morris, Huw R
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2013
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Brain Chemistry - genetics; Case-Control Studies; Female; Gene Expression Regulation; Globus Pallidus - metabolism; Globus Pallidus - pathology; Humans; Internal Medicine; Male; MAPT; Middle Aged; Neurology; Progressive supranuclear palsy; Protein Isoforms - biosynthesis; Protein Isoforms - genetics; Supranuclear Palsy, Progressive - diagnosis; Supranuclear Palsy, Progressive - genetics; Supranuclear Palsy, Progressive - metabolism; tau Proteins - biosynthesis; tau Proteins - genetics; Tauopathies; Young Adult; Tauopathies; Progressive supranuclear palsy; MAPT
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2013.01.017

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.