TY - JOUR
T1 - Variation in tau isoform expression in different brain regions and disease states
AU - Majounie, Elisa
AU - Cross, William
AU - Newsway, Victoria
AU - Dillman, Allissa
AU - Vandrovcova, Jana
AU - Morris, Christopher M.
AU - Nalls, Michael A.
AU - Ferrucci, Luigi
AU - Owen, Michael J.
AU - O'Donovan, Michael C.
AU - Cookson, Mark R.
AU - Singleton, Andrew B.
AU - de Silva, Rohan
AU - Morris, Huw R.
PY - 2013/7
Y1 - 2013/7
N2 - 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.
AB - 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.
KW - MAPT
KW - Progressive supranuclear palsy
KW - Tauopathies
UR - http://www.scopus.com/inward/record.url?scp=84875861863&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875861863&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2013.01.017
DO - 10.1016/j.neurobiolaging.2013.01.017
M3 - Article
C2 - 23428180
AN - SCOPUS:84875861863
SN - 0197-4580
VL - 34
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 7
ER -