A population-based study of tau protein and ubiquitin in cerebrospinal fluid in 85-year-olds: relation to severity of dementia and cerebral atrophy, but not to the apolipoprotein E4 allele.
Recently, a series of both non-coding (intronic) and coding (exonic) mutations in the tau gene have been linked to a family of autosomal dominant dementias referred to as frontotemporal dementia-17.
We have assessed whether apolipoprotein E (ApoE) genotype influences the age of onset of dementia in a series of families with frontal temporal dementia with defined mutations in the tau gene.
The mutations associated with PSG and other atypical dementias can be subdivided into three groups according to their tau gene locations and effects on tau.
5' splice site mutations in tau associated with the inherited dementiaFTDP-17 affect a stem-loop structure that regulates alternative splicing of exon 10.
Among families, the symptomatology appears to vary in quality and severity in relation to the specific Tau gene mutation and often may include parkinsonism, supranuclear palsies, and/or myoclonus, in addition to dementia.
Frontotemporal dementia with parkinsonism (FTDP-17) is an autosomal dominant disorder that presents clinically with dementia, extrapyramidal signs, and behavioral disturbances in mid-life and progresses to death within 5 to 10 years.
Mutations in the tau protein gene have recently been found to cause familial fronto-temporal dementia in a number of kindreds demonstrating linkage to chromosome 17.
Thus, the existence of a yet unknown mechanism of neurodegeneration, other than via mutations near or within the microtubule-binding sites, or the exon 10 splice sites of the tau gene, has to be considered to explain dementia in this family.
The polymorphism of apolipoprotein E (apoE) has been recognized as a genetic risk factor in different neurodegenerative disorders, with or without tau protein- related neuropathology, but few published epidemiological data are available as concerns the association of different apoE alleles with two relatively rare forms of dementia, Pick's disease (PiD) and Huntington's disease (HD).
We genotyped all family members for microsatellite markers at the IBGC1 locus and polymorphisms of the ApoE, VLDL, alpha1-ACT, BChE-K, APP, PS1, PS2 and tau genes and tested these for linkage to IBGC, dementia and bipolar disorder.
An N279K missense mutation in exon 10 of the tau gene reported in an American family with pallidopontonigral degeneration (PPND family) was recently found in members of a French kindred with dementia and supranuclear palsy.