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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-10-3
pubmed:abstractText
Some cases of familial frontotemporal dementia (FTD) leading to frontotemporal lobar degeneration (FTLD) are caused by mutations in tau on chromosome 17 (FTDP-17). Certain mutations alter the ratio between four (4R tau) and three (3R tau) repeat tau isoforms whereas cases with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) mainly have 4R tau brain pathology. We assessed tau mRNA and protein levels in frontal cortex from 15 sporadic FTLD, 21 PSP, 5 CBD, 15 Alzheimer's disease (AD) and 16 control brains. Moreover, we investigated the disease association and possible tau splicing effects of the tau H1 haplotype. Cases with FTLD and PSP had lower tau mRNA levels than control brains. When analyzing 4R tau and 3R tau mRNA separately, control subjects displayed a 4R tau/3R tau ratio of 0.48. Surprisingly, FTLD brains displayed a more elevated ratio (1.32) than PSP brains (1.12). Also, several FTLD and PSP cases had higher 4R tau/3R tau mRNA than FTDP-17 cases, included as reference tissues, and the ratio increase was seen regardless of underlying histopathology, i.e. both for tau-positive and tau-negative FTLD cases. Furthermore, total tau protein levels were slightly decreased in both FTLD and AD as compared to control subjects. Finally, we confirmed the association of tau H1 with PSP, but could not find any haplotype-related effect on tau exon 10 splicing. In conclusion, we demonstrated increased but largely variable 4R tau/3R tau mRNA ratios in FTLD and PSP cases, suggesting heterogeneous pathophysiological processes within these disorders.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0001-6322
pubmed:author
pubmed:issnType
Print
pubmed:volume
114
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
471-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17721707-Aged, pubmed-meshheading:17721707-Aged, 80 and over, pubmed-meshheading:17721707-Alternative Splicing, pubmed-meshheading:17721707-Brain, pubmed-meshheading:17721707-DNA Mutational Analysis, pubmed-meshheading:17721707-Dementia, pubmed-meshheading:17721707-Female, pubmed-meshheading:17721707-Genetic Predisposition to Disease, pubmed-meshheading:17721707-Genetic Testing, pubmed-meshheading:17721707-Haplotypes, pubmed-meshheading:17721707-Humans, pubmed-meshheading:17721707-Male, pubmed-meshheading:17721707-Middle Aged, pubmed-meshheading:17721707-Mutation, pubmed-meshheading:17721707-Protein Isoforms, pubmed-meshheading:17721707-RNA, Messenger, pubmed-meshheading:17721707-Supranuclear Palsy, Progressive, pubmed-meshheading:17721707-Trinucleotide Repeats, pubmed-meshheading:17721707-Up-Regulation, pubmed-meshheading:17721707-tau Proteins
pubmed:year
2007
pubmed:articleTitle
Increase in the relative expression of tau with four microtubule binding repeat regions in frontotemporal lobar degeneration and progressive supranuclear palsy brains.
pubmed:affiliation
Harvard Medical School, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA. martin.ingelsson@pubcare.uu.se
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural