TY - JOUR
T1 - Genetic disorders with tau pathology
T2 - A review of the literature and report of two patients with tauopathy and positive family histories
AU - Tacik, Pawel
AU - Sanchez-Contreras, Monica
AU - Rademakers, Rosa
AU - Dickson, Dennis W.
AU - Wszolek, Zbigniew K.
N1 - Publisher Copyright:
© 2015 S. Karger AG, Basel.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Background: Tauopathies are a group of neurodegenerative disorders characterized by the pathological accumulation of hyperphosphorylated and insoluble tau protein within neurons and glia. Although most cases are sporadic, hereditary tauopathies have also been reported. Summary: In this article, we review genetic disorders in which tau pathology has been reported and present two novel families with primary tauopathies. Mutations in the microtubule-associated protein tau gene (MAPT) cause a small subset of primary tauopathies. Mutations in 21 other genes and an 18q deletion syndrome have also been reported to be associated with tau pathology reminiscent of Alzheimer's disease, corticobasal degeneration, progressive supranuclear palsy, argyrophilic grain disease or Pick's disease. In 8 of the 21 genes, tau pathology was only seen in cases with some 'specific' mutations. In the remaining genes, tau pathology, often in the form of Alzheimer-type neurofibrillary lesions, was a common finding but was 'not mutation specific'. The probands of the two families were diagnosed with progressive supranuclear palsy based on clinicopathological evaluation. Their family histories were relevant for parkinsonism in 3 siblings of family 1 and 1 brother and the father from family 2, but these were not autopsy-confirmed. DNA from the brains of the probands from these families was screened for MAPT and leucine-rich repeat kinase 2 gene mutations, but no mutations were identified. Key Messages: MAPT mutations are a cause of familial tauopathies, but other genes have also been associated with tau pathology. Novel genes still await discovery.
AB - Background: Tauopathies are a group of neurodegenerative disorders characterized by the pathological accumulation of hyperphosphorylated and insoluble tau protein within neurons and glia. Although most cases are sporadic, hereditary tauopathies have also been reported. Summary: In this article, we review genetic disorders in which tau pathology has been reported and present two novel families with primary tauopathies. Mutations in the microtubule-associated protein tau gene (MAPT) cause a small subset of primary tauopathies. Mutations in 21 other genes and an 18q deletion syndrome have also been reported to be associated with tau pathology reminiscent of Alzheimer's disease, corticobasal degeneration, progressive supranuclear palsy, argyrophilic grain disease or Pick's disease. In 8 of the 21 genes, tau pathology was only seen in cases with some 'specific' mutations. In the remaining genes, tau pathology, often in the form of Alzheimer-type neurofibrillary lesions, was a common finding but was 'not mutation specific'. The probands of the two families were diagnosed with progressive supranuclear palsy based on clinicopathological evaluation. Their family histories were relevant for parkinsonism in 3 siblings of family 1 and 1 brother and the father from family 2, but these were not autopsy-confirmed. DNA from the brains of the probands from these families was screened for MAPT and leucine-rich repeat kinase 2 gene mutations, but no mutations were identified. Key Messages: MAPT mutations are a cause of familial tauopathies, but other genes have also been associated with tau pathology. Novel genes still await discovery.
KW - Genetics
KW - Microtubule-associated protein tau gene
KW - Tau pathology
KW - Tauopathies
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U2 - 10.1159/000440840
DO - 10.1159/000440840
M3 - Article
C2 - 26550830
AN - SCOPUS:84956964312
SN - 1660-2854
VL - 16
SP - 12
EP - 21
JO - Neurodegenerative Diseases
JF - Neurodegenerative Diseases
IS - 1-2
ER -