Clinicopathologic heterogeneity in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) due to microtubule-associated protein tau (MAPT) p.P301L mutation, including a patient with globular glial tauopathy

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Abstract

Aim: The p.P301L mutation in microtubule-associated protein tau (MAPT) is a common cause of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We compare clinicopathologic features of five unrelated and three related (brother, sister and cousin) patients with FTDP-17 due to p.P301L mutation. Methods: Genealogical, clinical, neuropathologic and genetic data were reviewed from eight individuals. Results: The series consisted of five men and three women with an average age of death of 58 years (52–65 years) and average disease duration of 9 years (3–14 years). The first symptoms were those of behavioural variant frontotemporal dementia in seven patients and semantic variant of primary progressive aphasia in one. Three patients were homozygous for the MAPT H1 haplotype; five had H1/H2 genotype. The apolipoprotein E genotype was ϵ3/ϵ3 in seven and ϵ3/ϵ4 in one. The average brain weight was 1015 g (876–1188 g). All had frontotemporal lobar or more diffuse cortical atrophy. Except for one patient, the hippocampus and parahippocampal gyrus had minimal atrophy, whereas there was atrophy of middle and inferior temporal gyri. Dentate fascia neuronal dispersion was identified in three patients, two of whom had epilepsy. In one patient there was extensive white matter tau involvement with Gallyas-positive globular glial inclusions typical of globular glial tauopathy (GGT). Conclusions: This clinicopathologic study shows inter- and intra-familial clinicopathologic heterogeneity of FTDP-17 due to MAPT p.P301L mutation, including GGT in one patient.

Original languageEnglish (US)
Pages (from-to)200-214
Number of pages15
JournalNeuropathology and Applied Neurobiology
Volume43
Issue number3
DOIs
StatePublished - Apr 1 2017

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Tauopathies
Frontotemporal Dementia
Chromosomes, Human, Pair 17
Microtubule-Associated Proteins
Parkinsonian Disorders
Neuroglia
Mutation
Atrophy
Siblings
Primary Progressive Aphasia
Genotype
Parahippocampal Gyrus
Dentate Gyrus
Apolipoproteins E
Temporal Lobe
Semantics
Haplotypes
Epilepsy
Hippocampus
Weights and Measures

Keywords

  • frontotemporal dementia and parkinsonism linked to chromosome 17
  • frontotemporal lobar degeneration
  • globular glial tauopathy
  • hereditary tauopathies
  • microtubule-associated protein tau

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Neurology
  • Clinical Neurology
  • Physiology (medical)

Cite this

@article{bc3ad559b5184c77b56262d62854c2de,
title = "Clinicopathologic heterogeneity in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) due to microtubule-associated protein tau (MAPT) p.P301L mutation, including a patient with globular glial tauopathy",
abstract = "Aim: The p.P301L mutation in microtubule-associated protein tau (MAPT) is a common cause of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We compare clinicopathologic features of five unrelated and three related (brother, sister and cousin) patients with FTDP-17 due to p.P301L mutation. Methods: Genealogical, clinical, neuropathologic and genetic data were reviewed from eight individuals. Results: The series consisted of five men and three women with an average age of death of 58 years (52–65 years) and average disease duration of 9 years (3–14 years). The first symptoms were those of behavioural variant frontotemporal dementia in seven patients and semantic variant of primary progressive aphasia in one. Three patients were homozygous for the MAPT H1 haplotype; five had H1/H2 genotype. The apolipoprotein E genotype was ϵ3/ϵ3 in seven and ϵ3/ϵ4 in one. The average brain weight was 1015 g (876–1188 g). All had frontotemporal lobar or more diffuse cortical atrophy. Except for one patient, the hippocampus and parahippocampal gyrus had minimal atrophy, whereas there was atrophy of middle and inferior temporal gyri. Dentate fascia neuronal dispersion was identified in three patients, two of whom had epilepsy. In one patient there was extensive white matter tau involvement with Gallyas-positive globular glial inclusions typical of globular glial tauopathy (GGT). Conclusions: This clinicopathologic study shows inter- and intra-familial clinicopathologic heterogeneity of FTDP-17 due to MAPT p.P301L mutation, including GGT in one patient.",
keywords = "frontotemporal dementia and parkinsonism linked to chromosome 17, frontotemporal lobar degeneration, globular glial tauopathy, hereditary tauopathies, microtubule-associated protein tau",
author = "P. Tacik and M. Sanchez-Contreras and Michael Deture and Murray, {Melissa E} and Rademakers, {Rosa V} and Ross, {Owen A} and Wszolek, {Zbigniew K} and Parisi, {Joseph E} and Knopman, {David S} and Petersen, {Ronald Carl} and Dickson, {Dennis W}",
year = "2017",
month = "4",
day = "1",
doi = "10.1111/nan.12367",
language = "English (US)",
volume = "43",
pages = "200--214",
journal = "Neuropathology and Applied Neurobiology",
issn = "0305-1846",
publisher = "Wiley-Blackwell",
number = "3",

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TY - JOUR

T1 - Clinicopathologic heterogeneity in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) due to microtubule-associated protein tau (MAPT) p.P301L mutation, including a patient with globular glial tauopathy

AU - Tacik, P.

AU - Sanchez-Contreras, M.

AU - Deture, Michael

AU - Murray, Melissa E

AU - Rademakers, Rosa V

AU - Ross, Owen A

AU - Wszolek, Zbigniew K

AU - Parisi, Joseph E

AU - Knopman, David S

AU - Petersen, Ronald Carl

AU - Dickson, Dennis W

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Aim: The p.P301L mutation in microtubule-associated protein tau (MAPT) is a common cause of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We compare clinicopathologic features of five unrelated and three related (brother, sister and cousin) patients with FTDP-17 due to p.P301L mutation. Methods: Genealogical, clinical, neuropathologic and genetic data were reviewed from eight individuals. Results: The series consisted of five men and three women with an average age of death of 58 years (52–65 years) and average disease duration of 9 years (3–14 years). The first symptoms were those of behavioural variant frontotemporal dementia in seven patients and semantic variant of primary progressive aphasia in one. Three patients were homozygous for the MAPT H1 haplotype; five had H1/H2 genotype. The apolipoprotein E genotype was ϵ3/ϵ3 in seven and ϵ3/ϵ4 in one. The average brain weight was 1015 g (876–1188 g). All had frontotemporal lobar or more diffuse cortical atrophy. Except for one patient, the hippocampus and parahippocampal gyrus had minimal atrophy, whereas there was atrophy of middle and inferior temporal gyri. Dentate fascia neuronal dispersion was identified in three patients, two of whom had epilepsy. In one patient there was extensive white matter tau involvement with Gallyas-positive globular glial inclusions typical of globular glial tauopathy (GGT). Conclusions: This clinicopathologic study shows inter- and intra-familial clinicopathologic heterogeneity of FTDP-17 due to MAPT p.P301L mutation, including GGT in one patient.

AB - Aim: The p.P301L mutation in microtubule-associated protein tau (MAPT) is a common cause of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We compare clinicopathologic features of five unrelated and three related (brother, sister and cousin) patients with FTDP-17 due to p.P301L mutation. Methods: Genealogical, clinical, neuropathologic and genetic data were reviewed from eight individuals. Results: The series consisted of five men and three women with an average age of death of 58 years (52–65 years) and average disease duration of 9 years (3–14 years). The first symptoms were those of behavioural variant frontotemporal dementia in seven patients and semantic variant of primary progressive aphasia in one. Three patients were homozygous for the MAPT H1 haplotype; five had H1/H2 genotype. The apolipoprotein E genotype was ϵ3/ϵ3 in seven and ϵ3/ϵ4 in one. The average brain weight was 1015 g (876–1188 g). All had frontotemporal lobar or more diffuse cortical atrophy. Except for one patient, the hippocampus and parahippocampal gyrus had minimal atrophy, whereas there was atrophy of middle and inferior temporal gyri. Dentate fascia neuronal dispersion was identified in three patients, two of whom had epilepsy. In one patient there was extensive white matter tau involvement with Gallyas-positive globular glial inclusions typical of globular glial tauopathy (GGT). Conclusions: This clinicopathologic study shows inter- and intra-familial clinicopathologic heterogeneity of FTDP-17 due to MAPT p.P301L mutation, including GGT in one patient.

KW - frontotemporal dementia and parkinsonism linked to chromosome 17

KW - frontotemporal lobar degeneration

KW - globular glial tauopathy

KW - hereditary tauopathies

KW - microtubule-associated protein tau

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U2 - 10.1111/nan.12367

DO - 10.1111/nan.12367

M3 - Article

C2 - 27859539

AN - SCOPUS:85014744388

VL - 43

SP - 200

EP - 214

JO - Neuropathology and Applied Neurobiology

JF - Neuropathology and Applied Neurobiology

SN - 0305-1846

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