PMID- 10218629
OWN - NLM
STAT- MEDLINE
DCOM- 19990506
LR  - 20190513
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 58
IP  - 4
DP  - 1999 Apr
TI  - Tau pathology in a family with dementia and a P301L mutation in tau.
PG  - 335-45
AB  - Familial forms of frontotemporal dementia and parkinsonism linked to chromosome 
      17 (FTDP-17) have recently been associated with coding region and intronic 
      mutations in the tau gene. Here we report our findings on 2 affected siblings 
      from a family with early-onset dementia, characterized by extensive tau pathology 
      and a Pro to Leu mutation at codon 301 of tau. The proband, a 55-year-old woman, 
      and her 63-year-old brother died after a progressive dementing illness clinically 
      diagnosed as Alzheimer disease. Their mother, 2 sisters, maternal aunt and uncle, 
      and several cousins were also affected. Autopsy in both cases revealed 
      frontotemporal atrophy and degeneration of basal ganglia and substantia nigra. 
      Sequencing of exon 10 of the tau gene revealed a C to T transition at codon 301, 
      resulting in a Pro to Leu substitution. Widespread neuronal and glial inclusions, 
      neuropil threads, and astrocytic plaques similar to those seen in corticobasal 
      degeneration were labeled with a battery of antibodies to 
      phosphorylation-dependent and phosphorylation-independent epitopes spanning the 
      entire tau sequence. Isolated tau filaments had the morphology of narrow twisted 
      ribbons. Sarkosyl-insoluble tau exhibited 2 major bands of 64 and 68 kDa and a 
      minor 72 kDa band, similar to the pattern seen in a familial tauopathy associated 
      with an intronic tau mutation. These pathological tau bands predominantly 
      contained the subset of tau isoforms with 4 microtubule-binding repeats 
      selectively affected by the P301L missense mutation. Our findings emphasize the 
      phenotypic and genetic heterogeneity of tauopathies and highlight intriguing 
      links between FTDP-17 and other neurodegenerative diseases.
FAU - Mirra, S S
AU  - Mirra SS
AD  - Department of Pathology, State University of New York, Health Science Center at 
      Brooklyn, 11203, USA.
FAU - Murrell, J R
AU  - Murrell JR
FAU - Gearing, M
AU  - Gearing M
FAU - Spillantini, M G
AU  - Spillantini MG
FAU - Goedert, M
AU  - Goedert M
FAU - Crowther, R A
AU  - Crowther RA
FAU - Levey, A I
AU  - Levey AI
FAU - Jones, R
AU  - Jones R
FAU - Green, J
AU  - Green J
FAU - Shoffner, J M
AU  - Shoffner JM
FAU - Wainer, B H
AU  - Wainer BH
FAU - Schmidt, M L
AU  - Schmidt ML
FAU - Trojanowski, J Q
AU  - Trojanowski JQ
FAU - Ghetti, B
AU  - Ghetti B
LA  - eng
GR  - AG10124/AG/NIA NIH HHS/United States
GR  - AG10130/AG/NIA NIH HHS/United States
GR  - AG10133/AG/NIA NIH HHS/United States
GR  - etc.
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (DNA Probes)
RN  - 0 (Epitopes)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Atrophy
MH  - Blotting, Western
MH  - Canada
MH  - DNA Mutational Analysis
MH  - DNA Probes
MH  - Dementia/*genetics/pathology
MH  - Epitopes/genetics
MH  - Family Health
MH  - Female
MH  - France
MH  - Frontal Lobe/pathology
MH  - Humans
MH  - Male
MH  - Microscopy, Electron
MH  - Middle Aged
MH  - Neurofibrillary Tangles/chemistry/ultrastructure
MH  - Neurons/*chemistry/*pathology
MH  - Parietal Lobe/pathology
MH  - Parkinson Disease/genetics/pathology
MH  - Pedigree
MH  - *Point Mutation
MH  - Polymerase Chain Reaction
MH  - Restriction Mapping
MH  - Solubility
MH  - Temporal Lobe/pathology
MH  - tau Proteins/analysis/*genetics
EDAT- 1999/04/28 00:00
MHDA- 1999/04/28 00:01
CRDT- 1999/04/28 00:00
PHST- 1999/04/28 00:00 [pubmed]
PHST- 1999/04/28 00:01 [medline]
PHST- 1999/04/28 00:00 [entrez]
AID - 10.1097/00005072-199904000-00004 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 1999 Apr;58(4):335-45. doi: 
      10.1097/00005072-199904000-00004.