All MAPT out?: Well-travelled pathways into neurodegeneration

Neurodegenerative disorders are characterized pathologically by insoluble protein aggregates in the neurons of affected brain regions. A common theme in neurodegenerative disease which has emerged is that mutations in the genes encoding the abnormally deposited protein cause autosomal-dominant inherited forms of disease. More recently, it has become apparent that common genetic variance at the same loci that cause Mendelian disease predispose risk to sporadic disease, generally by altering the expression levels of wild-type protein. The microtubule-associated protein tau (MAPT) is a classical example of this principle, and in this article, we discuss the biology and genetics of MAPT in disease, and compare and contrast MAPT with other loci implicated in neurodegeneration.