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   TAU MUTATIONS IN FTDP-17         

Tau pathology and tauopathies

Frontotemporal dementia with parkinsonism are caused by mutations on tau gene.

Author: Luc Buée, Inserm 422

In this figure is reported the location of mutations on exons (E9 to E12), on repeats (R) or inter-repeat (IR), provoking an increase of isoforms with exon 10 (+), or a loss of function (-), with a significant decrease of tau binding to tubulin dimers.

Clinical and neuropathological phenotypes are very different according to the mutations, as well as the biochemical signatures. Furthermore, for a given mutation, there is an important heterogenity of the clinical phenotype, inside the same family.

Explanation for tau biochemical signatures, from type I to type IV, click here

 

Mutation Localisation Splice E10 MT<->tau Phenotype Bioch. Signature Remark
R5H E1 ? ? Late Alzheimer Doublet PSP  
K257T E9, R1 = - Pick Doublet Pick Pick-like region
1260V E9, R1 ? ? ? ?  
L266V E9, R1  =   Pick like    
G272V E9, R1 = - FTDP-17, Pick-like Triplet Alzh.  
N279K E10, IR1-2 + = PSP Doublet PSP 4R impact
DK280 E10, IR1-2 - - FTDP-17 ?  
L284L E10, IR1-2 + = Alzheimer Doublet PSP Note the PSP phenotype for
N296N E10, R2 + = CBD Doublet PSP? all E10 or I10 mutations
DN296 E10, R2 + - PSP ?  
N296H E10, R2 + - FTDP-17 ?  
P301L E10, R2 = - PSP/CBD Doublet PSP  
P301S E10, R2 = - PSP/CBD Doublet PSP  
S305N E10, IR2-3 + + CBD Doublet PSP  
S305S E10, IR2-3 + = PSP Doublet PSP  
3 I10 + = FTDP-17 Doublet PSP abnormal splicing region
12 I10 + = FTDP-17 Doublet PSP (mutation in the intron of E10)
13 I10 + = ? Doublet PSP  
14 I10 + = PSP Doublet PSP  
16 I10 + = PSP, CBD Doublet PSP  
33 I10 ? ? ? ?  
S320Y E11 = - Pick Doublet Pick  
V337M E12, IR3-4 = - FTDP-17 Triplet Alzh.  
E342V E12, IR3-4 +? ? FTDP-17 ?  
K369I E12 R4 = - FTDP-17/Pick Triplet Alzh.  
G389R E13 = - Pick Doublet Pick  
R406W E13 = - PSP Triplet Alzh.