Progress and Prospects in Parkinson's Research/Causes/Inheritance/MAPT

The MAPT gene has been implicated in the onset of some types of familial Parkinson’s Disease.

General data

Its full official name is Microtubule-Associated Protein Tau.

Like many other genes MAPT is known by more than one name. Alternative names are:-

• TAU
• MTBT2
• FTDP-17
• FLJ31424
• MSTD
• PPND
• DDPAC
• MAPTL
• MTBT1
• STU/MAPT

In the human genome MAPT is to be found on the long arm of chromosome 17.

The cytogenetic location is 17q21.31.

The molecular base pairs are from 43,971,747 to 44,105,699.

The PD Gene database (2011) lists 36 Polymorphisms for this gene, of which 29 are termed ‘Significant’. It also cites 87 Caucasian gene association studies, 1 African descent gene association study,9 Asian gene association studies, 3 Other/Mixed gene association studies and 6 Caucasian Family-based studies.

What does MAPT do?

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.

The effect of Mutations

2005

Tobin et al evaluated the association of the MAPT region with PD in a large cohort of familial PD cases. They found that SNP rs1800547 was significantly associated with PD affection and the H1 haplotype was associated with a significantly increased risk for PD.

2010

Edwards et al carried out a genome-wide association study for PD with a cohort of 1752 cases and 1745 controls. SNPs in SNCA (rs2736990}, and the MAPT region (rs11012} were found to have an increased risk for PD.

Wray & Lewis have specified the role of this gene thus:-

In the adult human CNS, tau exists as six protein isoforms which differ by the presence of either 0, 1, or 2 N-terminal inserts and either three (3R) or four (4R) microtubule binding repeats located at the C terminus of the protein. Tau binds to and stabilizes microtubules via its C-terminal repeats in a process regulated by phosphorylation, where the phosphorylation of tau at specific residues favors its detachment from the microtubules.

and later:-

In PD, variation at the SNCA locus has been shown to act synergistically with variation at MAPT to increase disease risk, i.e., the increase in risk when carrying both risk variants is greater than the additive risk of carrying each variant in isolation. In vitro work has shown that α-synuclein and tau are able to influence each other's polymerization, and diffuse tau pathology is observed in transgenic mice expressing the α-synuclein A53T mutation.

MAPT gene mutations have been associated with several neurodegenerative disorders such as Alzheimer's disease, Pick's disease, frontotemporal dementia, cortico-basal degeneration and progressive supranuclear palsy

Further reading

MAPT Gene card http://www.genecards.org/cgi-bin/carddisp.pl?gene=MAPT

NCBI report http://www.ncbi.nlm.nih.gov/gene/4137

Related Pages

Causes > Inheritance

Sub Pages:

SNCA - LRRK2 - MAPT - GBA - HLA

Today

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