PMID- 10899436
OWN - NLM
STAT- MEDLINE
DCOM- 20000925
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1502
IP  - 1
DP  - 2000 Jul 26
TI  - Tau mutations in frontotemporal dementia FTDP-17 and their relevance for 
      Alzheimer's disease.
PG  - 110-21
AB  - Alzheimer's disease is characterised by the degeneration of selected populations 
      of nerve cells that develop filamentous inclusions prior to degeneration. The 
      neuronal inclusions of Alzheimer's disease are made of the microtubule-associated 
      protein tau, in a hyperphosphorylated state. Abundant filamentous tau inclusions 
      are not limited to Alzheimer's disease. They are the defining neuropathological 
      characteristic of frontotemporal dementias, such as Pick's disease, and of 
      progressive supranuclear palsy and corticobasal degeneration. The discovery of 
      mutations in the tau gene in familial frontotemporal dementia and parkinsonism 
      linked to chromosome 17 (FTDP-17) has provided a direct link between tau 
      dysfunction and dementing disease. Known mutations produce either a reduced 
      ability of tau to interact with microtubules, or an overproduction of tau 
      isoforms with four microtubule-binding repeats. This leads in turn to the 
      assembly of tau into filaments similar or identical to those found in Alzheimer's 
      disease brain. Several missense mutations also have a stimulatory effect on 
      heparin-induced tau filament formation. Assembly of tau into filaments may be the 
      gain of toxic function that is believed to underlie the demise of affected brain 
      cells.
FAU - Goedert, M
AU  - Goedert M
AD  - Medical Research Council Laboratory of Molecular Biology, Cambridge, UK. 
      mg@mrc-lmb.cam.ac.uk
FAU - Spillantini, M G
AU  - Spillantini MG
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 (Phosphoproteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Age of Onset
MH  - Alzheimer Disease/*genetics/pathology
MH  - Brain/metabolism/pathology
MH  - Dementia/*genetics/pathology
MH  - Exons
MH  - Humans
MH  - Introns
MH  - Microtubule-Associated Proteins/*genetics
MH  - Microtubules/ultrastructure
MH  - *Mutation
MH  - Phosphoproteins/metabolism
MH  - Protein Isoforms/metabolism
MH  - tau Proteins/*genetics/metabolism/ultrastructure
RF  - 103
EDAT- 2000/07/19 11:00
MHDA- 2000/09/30 11:01
CRDT- 2000/07/19 11:00
PHST- 2000/07/19 11:00 [pubmed]
PHST- 2000/09/30 11:01 [medline]
PHST- 2000/07/19 11:00 [entrez]
AID - S0925-4439(00)00037-5 [pii]
AID - 10.1016/s0925-4439(00)00037-5 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2000 Jul 26;1502(1):110-21. doi: 
      10.1016/s0925-4439(00)00037-5.