FTDP-17 with Pick body-like inclusions associated with a novel tau mutation, p.E372G

Pawel Tacik, Michael Deture, Yari Carlomagno, Wen Lang Lin, Melissa E Murray, Matthew C. Baker, Keith Anthony Josephs, Bradley F Boeve, Zbigniew K Wszolek, Neill R Graff Radford, Joseph E Parisi, Leonard Petrucelli, Rosa V Rademakers, Richard S. Isaacson, Kenneth M. Heilman, Ronald Carl Petersen, Dennis W Dickson, Naomi Kouri

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Mutations in microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). Here, we describe a patient with FTDP-17 and a novel missense mutation in exon 13 of MAPT, p.E372G. We compare clinicopathologic features of this patient to two previously unreported patients with another exon 13 mutation, p.G389R. The patient with the p.E372G mutation was a 40-year-old man with behavioral variant frontotemporal dementia (bvFTD), who subsequently developed agrammatic speech and parkinsonism. One of the FTDP-17 patients with p.G389R mutation presented at age 24 with agrammatic variant of primary progressive aphasia, and subsequently behavioral dysfunction. The other presented at age 53 with bvFTD, followed by agrammatic speech and corticobasal syndrome. Neuropathologic features of FTDP-17 due to p.E372G were similar to those of p.G389R, including tau-immunoreactive Pick body-like neuronal inclusions and swollen, tapering thread-like processes in white matter immunoreactive for 3-repeat and 4-repeat tau. Biochemical analysis of insoluble tau showed similar isoform compositions in p.E372G and p.G389R. Functional studies of the p.E372G mutation showed marked increase in tau filament formation and its reduced ability to promote microtubule assembly. Together these findings indicate that p.E372G is a pathogenic MAPT mutation that causes FTDP-17 similar to p.G389R.

Original languageEnglish (US)
JournalBrain Pathology
DOIs
StateAccepted/In press - 2016

Fingerprint

Frontotemporal Dementia
Inclusion Bodies
Mutation
Microtubule-Associated Proteins
Exons
Primary Progressive Aphasia
Genes
Chromosomes, Human, Pair 17
Aptitude
Parkinsonian Disorders
Missense Mutation
Microtubules
Protein Isoforms

Keywords

  • Frontotemporal dementia
  • FTDP-17
  • MAPT mutations
  • Pick's disease
  • Primary progressive aphasia

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

Cite this

FTDP-17 with Pick body-like inclusions associated with a novel tau mutation, p.E372G. / Tacik, Pawel; Deture, Michael; Carlomagno, Yari; Lin, Wen Lang; Murray, Melissa E; Baker, Matthew C.; Josephs, Keith Anthony; Boeve, Bradley F; Wszolek, Zbigniew K; Graff Radford, Neill R; Parisi, Joseph E; Petrucelli, Leonard; Rademakers, Rosa V; Isaacson, Richard S.; Heilman, Kenneth M.; Petersen, Ronald Carl; Dickson, Dennis W; Kouri, Naomi.

In: Brain Pathology, 2016.

Research output: Contribution to journalArticle

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abstract = "Mutations in microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). Here, we describe a patient with FTDP-17 and a novel missense mutation in exon 13 of MAPT, p.E372G. We compare clinicopathologic features of this patient to two previously unreported patients with another exon 13 mutation, p.G389R. The patient with the p.E372G mutation was a 40-year-old man with behavioral variant frontotemporal dementia (bvFTD), who subsequently developed agrammatic speech and parkinsonism. One of the FTDP-17 patients with p.G389R mutation presented at age 24 with agrammatic variant of primary progressive aphasia, and subsequently behavioral dysfunction. The other presented at age 53 with bvFTD, followed by agrammatic speech and corticobasal syndrome. Neuropathologic features of FTDP-17 due to p.E372G were similar to those of p.G389R, including tau-immunoreactive Pick body-like neuronal inclusions and swollen, tapering thread-like processes in white matter immunoreactive for 3-repeat and 4-repeat tau. Biochemical analysis of insoluble tau showed similar isoform compositions in p.E372G and p.G389R. Functional studies of the p.E372G mutation showed marked increase in tau filament formation and its reduced ability to promote microtubule assembly. Together these findings indicate that p.E372G is a pathogenic MAPT mutation that causes FTDP-17 similar to p.G389R.",
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author = "Pawel Tacik and Michael Deture and Yari Carlomagno and Lin, {Wen Lang} and Murray, {Melissa E} and Baker, {Matthew C.} and Josephs, {Keith Anthony} and Boeve, {Bradley F} and Wszolek, {Zbigniew K} and {Graff Radford}, {Neill R} and Parisi, {Joseph E} and Leonard Petrucelli and Rademakers, {Rosa V} and Isaacson, {Richard S.} and Heilman, {Kenneth M.} and Petersen, {Ronald Carl} and Dickson, {Dennis W} and Naomi Kouri",
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T1 - FTDP-17 with Pick body-like inclusions associated with a novel tau mutation, p.E372G

AU - Tacik, Pawel

AU - Deture, Michael

AU - Carlomagno, Yari

AU - Lin, Wen Lang

AU - Murray, Melissa E

AU - Baker, Matthew C.

AU - Josephs, Keith Anthony

AU - Boeve, Bradley F

AU - Wszolek, Zbigniew K

AU - Graff Radford, Neill R

AU - Parisi, Joseph E

AU - Petrucelli, Leonard

AU - Rademakers, Rosa V

AU - Isaacson, Richard S.

AU - Heilman, Kenneth M.

AU - Petersen, Ronald Carl

AU - Dickson, Dennis W

AU - Kouri, Naomi

PY - 2016

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N2 - Mutations in microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). Here, we describe a patient with FTDP-17 and a novel missense mutation in exon 13 of MAPT, p.E372G. We compare clinicopathologic features of this patient to two previously unreported patients with another exon 13 mutation, p.G389R. The patient with the p.E372G mutation was a 40-year-old man with behavioral variant frontotemporal dementia (bvFTD), who subsequently developed agrammatic speech and parkinsonism. One of the FTDP-17 patients with p.G389R mutation presented at age 24 with agrammatic variant of primary progressive aphasia, and subsequently behavioral dysfunction. The other presented at age 53 with bvFTD, followed by agrammatic speech and corticobasal syndrome. Neuropathologic features of FTDP-17 due to p.E372G were similar to those of p.G389R, including tau-immunoreactive Pick body-like neuronal inclusions and swollen, tapering thread-like processes in white matter immunoreactive for 3-repeat and 4-repeat tau. Biochemical analysis of insoluble tau showed similar isoform compositions in p.E372G and p.G389R. Functional studies of the p.E372G mutation showed marked increase in tau filament formation and its reduced ability to promote microtubule assembly. Together these findings indicate that p.E372G is a pathogenic MAPT mutation that causes FTDP-17 similar to p.G389R.

AB - Mutations in microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). Here, we describe a patient with FTDP-17 and a novel missense mutation in exon 13 of MAPT, p.E372G. We compare clinicopathologic features of this patient to two previously unreported patients with another exon 13 mutation, p.G389R. The patient with the p.E372G mutation was a 40-year-old man with behavioral variant frontotemporal dementia (bvFTD), who subsequently developed agrammatic speech and parkinsonism. One of the FTDP-17 patients with p.G389R mutation presented at age 24 with agrammatic variant of primary progressive aphasia, and subsequently behavioral dysfunction. The other presented at age 53 with bvFTD, followed by agrammatic speech and corticobasal syndrome. Neuropathologic features of FTDP-17 due to p.E372G were similar to those of p.G389R, including tau-immunoreactive Pick body-like neuronal inclusions and swollen, tapering thread-like processes in white matter immunoreactive for 3-repeat and 4-repeat tau. Biochemical analysis of insoluble tau showed similar isoform compositions in p.E372G and p.G389R. Functional studies of the p.E372G mutation showed marked increase in tau filament formation and its reduced ability to promote microtubule assembly. Together these findings indicate that p.E372G is a pathogenic MAPT mutation that causes FTDP-17 similar to p.G389R.

KW - Frontotemporal dementia

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KW - Pick's disease

KW - Primary progressive aphasia

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