Genetic disorders with tau pathology: A review of the literature and report of two patients with tauopathy and positive family histories

Pawel Tacik, Monica Sanchez-Contreras, Rosa V Rademakers, Dennis W Dickson, Zbigniew K Wszolek

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)12-21
Number of pages10
JournalNeurodegenerative Diseases
Volume16
Issue number1-2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Tauopathies
Inborn Genetic Diseases
Pathology
Mutation
Genes
Microtubule-Associated Proteins
Progressive Supranuclear Palsy
Siblings
Pick Disease of the Brain
tau Proteins
Gene Deletion
Parkinsonian Disorders
Leucine
Neuroglia
Fathers
Neurodegenerative Diseases
Autopsy
Alzheimer Disease
Phosphotransferases
Neurons

Keywords

  • Genetics
  • Microtubule-associated protein tau gene
  • Tau pathology
  • Tauopathies

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

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title = "Genetic disorders with tau pathology: A review of the literature and report of two patients with tauopathy and positive family histories",
abstract = "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.",
keywords = "Genetics, Microtubule-associated protein tau gene, Tau pathology, Tauopathies",
author = "Pawel Tacik and Monica Sanchez-Contreras and Rademakers, {Rosa V} and Dickson, {Dennis W} and Wszolek, {Zbigniew K}",
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AU - Wszolek, Zbigniew K

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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

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