Neurodegenerative disease phenotypes in carriers of MAPT P.A152T, a risk factor for frontotemporal dementia spectrum disorders and alzheimer disease

Suzee E. Lee, Maria C. Tartaglia, Görsev Yener, Sermin Genç, William W. Seeley, Pascual Sanchez-Juan, Fermin Moreno, Mario F. Mendez, Eric Klein, Rosa V Rademakers, Adolfo López De Munain, Onofre Combarros, Joel H. Kramer, Robert O. Kenet, Adam L. Boxer, Michael D. Geschwind, Maria Luisa Gorno-Tempini, Anna M. Karydas, Gil D. Rabinovici, Giovanni CoppolaDaniel H. Geschwind, Bruce L. Miller

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Recently, Coppola and colleagues demonstrated that a rare microtubule-associated protein tau (MAPT) sequence variant, c.454G>A (p.A152T) significantly increases the risk of frontotemporal dementia (FTD) spectrum disorders and Alzheimer disease (AD) in a screen of 15,369 subjects. We describe clinical features of 9 patients with neurodegenerative disease (4 women) harboring p.A152T, aged 51 to 79 years at symptom onset. Seven developed FTD spectrum clinical syndromes, including progressive supranuclear palsy syndrome (n=2), behavioral variant FTD (bvFTD, n=1), nonfluent variant primary progressive aphasia (nfvPPA, n=2), and corticobasal syndrome (n=2); 2 patients were diagnosed with clinical AD. Thus, MAPT p.A152T is associated with a variety of FTD spectrum clinical presentations, although patients with clinical AD are also identified. These data warrant larger studies with clinicopathologic correlation to elucidate the influence of this genetic variant on neurodegenerative disease.

Original languageEnglish (US)
Pages (from-to)302-309
Number of pages8
JournalAlzheimer Disease and Associated Disorders
Volume27
Issue number4
DOIs
StatePublished - Oct 2013
Externally publishedYes

Fingerprint

Frontotemporal Dementia
Microtubule-Associated Proteins
Neurodegenerative Diseases
Alzheimer Disease
Phenotype
Primary Progressive Nonfluent Aphasia
Progressive Supranuclear Palsy

Keywords

  • all cognitive disorders/dementia
  • Alzheimer disease
  • corticobasal degeneration
  • frontotemporal dementia
  • progressive supranuclear palsy

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Gerontology
  • Clinical Psychology

Cite this

Neurodegenerative disease phenotypes in carriers of MAPT P.A152T, a risk factor for frontotemporal dementia spectrum disorders and alzheimer disease. / Lee, Suzee E.; Tartaglia, Maria C.; Yener, Görsev; Genç, Sermin; Seeley, William W.; Sanchez-Juan, Pascual; Moreno, Fermin; Mendez, Mario F.; Klein, Eric; Rademakers, Rosa V; Munain, Adolfo López De; Combarros, Onofre; Kramer, Joel H.; Kenet, Robert O.; Boxer, Adam L.; Geschwind, Michael D.; Gorno-Tempini, Maria Luisa; Karydas, Anna M.; Rabinovici, Gil D.; Coppola, Giovanni; Geschwind, Daniel H.; Miller, Bruce L.

In: Alzheimer Disease and Associated Disorders, Vol. 27, No. 4, 10.2013, p. 302-309.

Research output: Contribution to journalArticle

Lee, SE, Tartaglia, MC, Yener, G, Genç, S, Seeley, WW, Sanchez-Juan, P, Moreno, F, Mendez, MF, Klein, E, Rademakers, RV, Munain, ALD, Combarros, O, Kramer, JH, Kenet, RO, Boxer, AL, Geschwind, MD, Gorno-Tempini, ML, Karydas, AM, Rabinovici, GD, Coppola, G, Geschwind, DH & Miller, BL 2013, 'Neurodegenerative disease phenotypes in carriers of MAPT P.A152T, a risk factor for frontotemporal dementia spectrum disorders and alzheimer disease', Alzheimer Disease and Associated Disorders, vol. 27, no. 4, pp. 302-309. https://doi.org/10.1097/WAD.0b013e31828cc357
Lee, Suzee E. ; Tartaglia, Maria C. ; Yener, Görsev ; Genç, Sermin ; Seeley, William W. ; Sanchez-Juan, Pascual ; Moreno, Fermin ; Mendez, Mario F. ; Klein, Eric ; Rademakers, Rosa V ; Munain, Adolfo López De ; Combarros, Onofre ; Kramer, Joel H. ; Kenet, Robert O. ; Boxer, Adam L. ; Geschwind, Michael D. ; Gorno-Tempini, Maria Luisa ; Karydas, Anna M. ; Rabinovici, Gil D. ; Coppola, Giovanni ; Geschwind, Daniel H. ; Miller, Bruce L. / Neurodegenerative disease phenotypes in carriers of MAPT P.A152T, a risk factor for frontotemporal dementia spectrum disorders and alzheimer disease. In: Alzheimer Disease and Associated Disorders. 2013 ; Vol. 27, No. 4. pp. 302-309.
@article{de984a86e7a641aca2ec5bb9c75a5299,
title = "Neurodegenerative disease phenotypes in carriers of MAPT P.A152T, a risk factor for frontotemporal dementia spectrum disorders and alzheimer disease",
abstract = "Recently, Coppola and colleagues demonstrated that a rare microtubule-associated protein tau (MAPT) sequence variant, c.454G>A (p.A152T) significantly increases the risk of frontotemporal dementia (FTD) spectrum disorders and Alzheimer disease (AD) in a screen of 15,369 subjects. We describe clinical features of 9 patients with neurodegenerative disease (4 women) harboring p.A152T, aged 51 to 79 years at symptom onset. Seven developed FTD spectrum clinical syndromes, including progressive supranuclear palsy syndrome (n=2), behavioral variant FTD (bvFTD, n=1), nonfluent variant primary progressive aphasia (nfvPPA, n=2), and corticobasal syndrome (n=2); 2 patients were diagnosed with clinical AD. Thus, MAPT p.A152T is associated with a variety of FTD spectrum clinical presentations, although patients with clinical AD are also identified. These data warrant larger studies with clinicopathologic correlation to elucidate the influence of this genetic variant on neurodegenerative disease.",
keywords = "all cognitive disorders/dementia, Alzheimer disease, corticobasal degeneration, frontotemporal dementia, progressive supranuclear palsy",
author = "Lee, {Suzee E.} and Tartaglia, {Maria C.} and G{\"o}rsev Yener and Sermin Gen{\cc} and Seeley, {William W.} and Pascual Sanchez-Juan and Fermin Moreno and Mendez, {Mario F.} and Eric Klein and Rademakers, {Rosa V} and Munain, {Adolfo L{\'o}pez De} and Onofre Combarros and Kramer, {Joel H.} and Kenet, {Robert O.} and Boxer, {Adam L.} and Geschwind, {Michael D.} and Gorno-Tempini, {Maria Luisa} and Karydas, {Anna M.} and Rabinovici, {Gil D.} and Giovanni Coppola and Geschwind, {Daniel H.} and Miller, {Bruce L.}",
year = "2013",
month = "10",
doi = "10.1097/WAD.0b013e31828cc357",
language = "English (US)",
volume = "27",
pages = "302--309",
journal = "Alzheimer Disease and Associated Disorders",
issn = "0893-0341",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Neurodegenerative disease phenotypes in carriers of MAPT P.A152T, a risk factor for frontotemporal dementia spectrum disorders and alzheimer disease

AU - Lee, Suzee E.

AU - Tartaglia, Maria C.

AU - Yener, Görsev

AU - Genç, Sermin

AU - Seeley, William W.

AU - Sanchez-Juan, Pascual

AU - Moreno, Fermin

AU - Mendez, Mario F.

AU - Klein, Eric

AU - Rademakers, Rosa V

AU - Munain, Adolfo López De

AU - Combarros, Onofre

AU - Kramer, Joel H.

AU - Kenet, Robert O.

AU - Boxer, Adam L.

AU - Geschwind, Michael D.

AU - Gorno-Tempini, Maria Luisa

AU - Karydas, Anna M.

AU - Rabinovici, Gil D.

AU - Coppola, Giovanni

AU - Geschwind, Daniel H.

AU - Miller, Bruce L.

PY - 2013/10

Y1 - 2013/10

N2 - Recently, Coppola and colleagues demonstrated that a rare microtubule-associated protein tau (MAPT) sequence variant, c.454G>A (p.A152T) significantly increases the risk of frontotemporal dementia (FTD) spectrum disorders and Alzheimer disease (AD) in a screen of 15,369 subjects. We describe clinical features of 9 patients with neurodegenerative disease (4 women) harboring p.A152T, aged 51 to 79 years at symptom onset. Seven developed FTD spectrum clinical syndromes, including progressive supranuclear palsy syndrome (n=2), behavioral variant FTD (bvFTD, n=1), nonfluent variant primary progressive aphasia (nfvPPA, n=2), and corticobasal syndrome (n=2); 2 patients were diagnosed with clinical AD. Thus, MAPT p.A152T is associated with a variety of FTD spectrum clinical presentations, although patients with clinical AD are also identified. These data warrant larger studies with clinicopathologic correlation to elucidate the influence of this genetic variant on neurodegenerative disease.

AB - Recently, Coppola and colleagues demonstrated that a rare microtubule-associated protein tau (MAPT) sequence variant, c.454G>A (p.A152T) significantly increases the risk of frontotemporal dementia (FTD) spectrum disorders and Alzheimer disease (AD) in a screen of 15,369 subjects. We describe clinical features of 9 patients with neurodegenerative disease (4 women) harboring p.A152T, aged 51 to 79 years at symptom onset. Seven developed FTD spectrum clinical syndromes, including progressive supranuclear palsy syndrome (n=2), behavioral variant FTD (bvFTD, n=1), nonfluent variant primary progressive aphasia (nfvPPA, n=2), and corticobasal syndrome (n=2); 2 patients were diagnosed with clinical AD. Thus, MAPT p.A152T is associated with a variety of FTD spectrum clinical presentations, although patients with clinical AD are also identified. These data warrant larger studies with clinicopathologic correlation to elucidate the influence of this genetic variant on neurodegenerative disease.

KW - all cognitive disorders/dementia

KW - Alzheimer disease

KW - corticobasal degeneration

KW - frontotemporal dementia

KW - progressive supranuclear palsy

UR - http://www.scopus.com/inward/record.url?scp=84888132252&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888132252&partnerID=8YFLogxK

U2 - 10.1097/WAD.0b013e31828cc357

DO - 10.1097/WAD.0b013e31828cc357

M3 - Article

C2 - 23518664

AN - SCOPUS:84888132252

VL - 27

SP - 302

EP - 309

JO - Alzheimer Disease and Associated Disorders

JF - Alzheimer Disease and Associated Disorders

SN - 0893-0341

IS - 4

ER -