PMID- 11115852
OWN - NLM
STAT- MEDLINE
DCOM- 20010222
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 9
IP  - 20
DP  - 2000 Dec 12
TI  - Mutation-dependent aggregation of tau protein and its selective depletion from 
      the soluble fraction in brain of P301L FTDP-17 patients.
PG  - 3075-82
AB  - Mutations in the gene for the microtubule-associated protein tau are associated 
      with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). 
      In this study we compared the presence of the P301L mutated tau protein from 
      brain material of patients with that of the normal 4-repeat, using polyclonal 
      antibodies specific for the P301L point mutation and its normal counterpart. We 
      determined the relative ratio of mutated versus normal tau protein in the 
      sarkosyl-soluble and -insoluble protein fractions from several brain regions. 
      Although mutated and normal tau proteins are both present in the 
      sarkosyl-insoluble deposits, quantitative analysis showed that the mutated 
      protein is the major component. In the sarkosyl-soluble fraction of frontal and 
      temporal cortex the overall ratio of 3-repeat versus 4-repeat tau isoforms is 
      unchanged but there is a dramatic depletion of mutant tau protein. Furthermore, 
      we observed an increase in tau-immunoreactive cleavage products with the P301L 
      antibody, suggesting that the mutant protein is partly resistant to degradation 
      and this is confirmed by pulse-chase experiments. This is the first direct 
      evidence using patient material that shows a selective aggregation of mutant tau 
      protein resulting in sarkosyl-insoluble deposits and the specific depletion of 
      mutated tau protein in the soluble fraction.
FAU - Rizzu, P
AU  - Rizzu P
AD  - Department of Clinical Genetics, Erasmus University, PO Box 1738, 3000 DR 
      Rotterdam, The Netherlands.
FAU - Joosse, M
AU  - Joosse M
FAU - Ravid, R
AU  - Ravid R
FAU - Hoogeveen, A
AU  - Hoogeveen A
FAU - Kamphorst, W
AU  - Kamphorst W
FAU - van Swieten, J C
AU  - van Swieten JC
FAU - Willemsen, R
AU  - Willemsen R
FAU - Heutink, P
AU  - Heutink P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Antibodies)
RN  - 0 (MAPT protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Aged
MH  - Amino Acid Substitution
MH  - Animals
MH  - Antibodies
MH  - COS Cells
MH  - Cerebral Cortex/*metabolism
MH  - Chromosomes, Human, Pair 17
MH  - Dementia/*genetics/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Microtubule-Associated Proteins/*genetics/immunology
MH  - Middle Aged
MH  - PC12 Cells
MH  - Parkinsonian Disorders/*genetics/metabolism
MH  - Point Mutation
MH  - Prefrontal Cortex/metabolism
MH  - Rabbits
MH  - Rats
MH  - tau Proteins/*genetics/immunology
EDAT- 2000/12/15 11:00
MHDA- 2001/03/03 10:01
CRDT- 2000/12/15 11:00
PHST- 2000/12/15 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/12/15 11:00 [entrez]
AID - 10.1093/hmg/9.20.3075 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2000 Dec 12;9(20):3075-82. doi: 10.1093/hmg/9.20.3075.