| This gene encodes the microtubule-associated protein tau (MAPT) whose transcript undergoes complex, regulated alternative splicing, giving rise to several mRNA species. MAPT transcripts are differentially expressed in the nervous system, depending on stage of neuronal maturation and neuron type. MAPT gene mutations have been associated with several neurodegenerative disorders such as Alzheimers disease, Picks disease, frontotemporal dementia, cortico-basal degeneration and progressive supranuclear palsy. [provided by RefSeq, Jul 2008],alternative products:Additional isoforms seem to exist. Isoforms differ from each other by the presence or absence of up to 5 of the 15 exons. One of these optional exons contains the additional tau/MAP repeat,developmental stage:Four-repeat (type II) tau is expressed in an adult-specific manner and is not found in fetal brain, whereas three-repeat (type I) tau is found in both adult and fetal brain.,disease:Defects in MAPT are a cause of corticobasal degeneration (CBD). It is marked by extrapyramidal signs and apraxia and can be associated with memory loss. Neuropathologic features may overlap Alzheimer disease, progressive supranuclear palsy, and Parkinson disease.,disease:Defects in MAPT are a cause of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP17) [MIM:600274, 172700], also called frontotemporal dementia (FTD) or historically termed Pick complex. This form of frontotemporal dementia is characterized by presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons.,disease:Defects in MAPT are a cause of pallido-ponto-nigral degeneration (PPND) [MIM:168610]. The clinical features include ocular motility abnormalities, dystonia and urinary incontinence, besides progressive parkinsonism and dementia.,disease:Defects in MAPT are a cause of progressive supranuclear palsy (PSP) [MIM:601104, 260540], also known as Steele-Richardson-Olszewski syndrome. PSP is characterized by akinetic-rigid syndrome, supranuclear gaze palsy, pyramidal tract dysfunction, pseudobulbar signs and cognitive capacities deterioration. Neurofibrillary tangles and gliosis but no amyloid plaques are found in diseased brains. Most cases appear to be sporadic, with a significant association with a common haplotype including the MAPT gene and the flanking regions. Familial cases show an autosomal dominant pattern of transmission with incomplete penetrance, genetic analysis of a few cases showed the occurrence of tau mutations, including a deletion of Asn-613.,disease:Defects in MAPT may be a cause of hereditary dysphasic disinhibition dementia (HDDD) [MIM:607485]. HDDD is a frontotemporal dementia characterized by progressive cognitive deficits with memory loss and personality changes, severe dysphasic disturbances leading to mutism, and hyperphagia.,disease:In Alzheimer disease, the neuronal cytoskeleton in the brain is progressively disrupted and replaced by tangles of paired helical filaments (PHF) and straight filaments, mainly composed of hyperphosphorylated forms of TAU (PHF-TAU or AD P-TAU).,domain:The tau/MAP repeat binds to tubulin. Type I isoforms contain 3 repeats while type II isoforms contain 4 repeats.,function:Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both. Axonal polarity is predetermined by tau localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton where |
