PMID- 15615630
OWN - NLM
STAT- MEDLINE
DCOM- 20050203
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1739
IP  - 2-3
DP  - 2005 Jan 3
TI  - Regulation of tau isoform expression and dementia.
PG  - 104-15
AB  - In the central nervous system (CNS), aberrant changes in tau mRNA splicing and 
      consequently in protein isoform ratios cause abnormal aggregation of tau and 
      neurodegeneration. Pathological tau causes neuronal loss in Alzheimer's disease 
      (AD) and a diverse group of disorders called the frontotemporal dementias (FTD), 
      which are two of the most common forms of dementia and afflict more than 10% of 
      the elderly population. Autosomal dominant mutations in the tau gene cause 
      frontotemporal dementia with parkinsonism-chromosome 17 type (FTDP-17). Just over 
      half the mutations affect tau protein function and decrease its affinity for 
      microtubules (MTs) or increase self-aggregation. The remaining mutations occur 
      within exon 10 (E10) and intron 10 sequences and alter complex regulation of E10 
      splicing by multiple mechanisms. FTDP-17 splicing mutations disturb the normally 
      balanced levels of distinct protein isoforms that result in altered biochemical 
      and structural properties of tau. In addition to FTDP-17, altered tau isoform 
      levels are also pathogenically associated with other FTD disorders such as 
      progressive supranuclear palsy (PSP), corticobasal degeneration and Pick's 
      disease; however, the mechanisms remain undefined and mutations in tau have not 
      been detected. FTDP-17 highlights the association between splicing mutations and 
      the pronounced variability in pathology as well as phenotype that is 
      characteristic of inherited disorders.
FAU - D'Souza, Ian
AU  - D'Souza I
AD  - Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound 
      Health Care System, Seattle Division, 1660 S. Columbian Way, Seattle, WA 98108, 
      USA.
FAU - Schellenberg, Gerard D
AU  - Schellenberg GD
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (MAPT protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (tau Proteins)
SB  - IM
MH  - *Alternative Splicing
MH  - Base Sequence
MH  - Dementia/*genetics
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Microtubule-Associated Proteins/genetics
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Nerve Tissue Proteins/genetics
MH  - Protein Isoforms/genetics
MH  - Tauopathies/genetics
MH  - tau Proteins/*genetics
RF  - 117
EDAT- 2004/12/24 09:00
MHDA- 2005/02/04 09:00
CRDT- 2004/12/24 09:00
PHST- 2004/08/17 00:00 [received]
PHST- 2004/08/24 00:00 [accepted]
PHST- 2004/12/24 09:00 [pubmed]
PHST- 2005/02/04 09:00 [medline]
PHST- 2004/12/24 09:00 [entrez]
AID - S0925-4439(04)00152-8 [pii]
AID - 10.1016/j.bbadis.2004.08.009 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2005 Jan 3;1739(2-3):104-15. doi: 
      10.1016/j.bbadis.2004.08.009.