Atrophy patterns in IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M MAPT mutations

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Abstract

OBJECTIVE: To use a case-control study to assess and compare patterns of gray matter loss across groups of subjects with different mutations in the microtubule-associated protein tau (MAPT) gene. METHODS: We identified all subjects from Mayo Clinic, Rochester, Minnesota, that screened positive for mutations in MAPT and had a head MRI (n = 22). Voxel-based morphometry was used to assess patterns of gray matter atrophy in groups of subjects with the IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M mutations compared with age-and sex-matched controls. RESULTS: All MAPT groups showed gray matter loss in the anterior temporal lobes, with varying degrees of involvement of the frontal and parietal lobes. Within the temporal lobe, the subjects with IVS10+16, IVS10+3, N279K, and S305N mutations (mutations that influence the alternative splicing of tau pre-messenger RNA) all showed gray matter loss focused on the medial temporal lobes. In contrast to these groups, the subjects with P301L or V337M mutations (mutations that affect the structure of the tau protein) both showed gray matter loss focused on the lateral temporal lobes, with a relative sparing of the medial temporal lobe. CONCLUSION: There seem to be differences in patterns of temporal lobe atrophy across the MAPT mutations, which may aid in the differentiation of the different mutation carriers. Furthermore, there seems to be a possible association between mutation function and pattern of temporal lobe atrophy.

Original languageEnglish (US)
Pages (from-to)1058-1065
Number of pages8
JournalNeurology
Volume73
Issue number13
DOIs
StatePublished - Sep 2009

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Microtubule-Associated Proteins
Atrophy
Temporal Lobe
Mutation
tau Proteins
Parietal Lobe
Alternative Splicing
Frontal Lobe
Case-Control Studies
Head
Gray Matter
Messenger RNA

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

@article{96e46676829c4304ae77e8c67d9b91e4,
title = "Atrophy patterns in IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M MAPT mutations",
abstract = "OBJECTIVE: To use a case-control study to assess and compare patterns of gray matter loss across groups of subjects with different mutations in the microtubule-associated protein tau (MAPT) gene. METHODS: We identified all subjects from Mayo Clinic, Rochester, Minnesota, that screened positive for mutations in MAPT and had a head MRI (n = 22). Voxel-based morphometry was used to assess patterns of gray matter atrophy in groups of subjects with the IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M mutations compared with age-and sex-matched controls. RESULTS: All MAPT groups showed gray matter loss in the anterior temporal lobes, with varying degrees of involvement of the frontal and parietal lobes. Within the temporal lobe, the subjects with IVS10+16, IVS10+3, N279K, and S305N mutations (mutations that influence the alternative splicing of tau pre-messenger RNA) all showed gray matter loss focused on the medial temporal lobes. In contrast to these groups, the subjects with P301L or V337M mutations (mutations that affect the structure of the tau protein) both showed gray matter loss focused on the lateral temporal lobes, with a relative sparing of the medial temporal lobe. CONCLUSION: There seem to be differences in patterns of temporal lobe atrophy across the MAPT mutations, which may aid in the differentiation of the different mutation carriers. Furthermore, there seems to be a possible association between mutation function and pattern of temporal lobe atrophy.",
author = "Whitwell, {Jennifer Lynn} and Jack, {Clifford R Jr.} and Boeve, {Bradley F} and Senjem, {M. L.} and M. Baker and Ivnik, {R. J.} and Knopman, {David S} and Wszolek, {Zbigniew K} and Petersen, {Ronald Carl} and Rademakers, {Rosa V} and Josephs, {Keith Anthony}",
year = "2009",
month = "9",
doi = "10.1212/WNL.0b013e3181b9c8b9",
language = "English (US)",
volume = "73",
pages = "1058--1065",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "13",

}

TY - JOUR

T1 - Atrophy patterns in IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M MAPT mutations

AU - Whitwell, Jennifer Lynn

AU - Jack, Clifford R Jr.

AU - Boeve, Bradley F

AU - Senjem, M. L.

AU - Baker, M.

AU - Ivnik, R. J.

AU - Knopman, David S

AU - Wszolek, Zbigniew K

AU - Petersen, Ronald Carl

AU - Rademakers, Rosa V

AU - Josephs, Keith Anthony

PY - 2009/9

Y1 - 2009/9

N2 - OBJECTIVE: To use a case-control study to assess and compare patterns of gray matter loss across groups of subjects with different mutations in the microtubule-associated protein tau (MAPT) gene. METHODS: We identified all subjects from Mayo Clinic, Rochester, Minnesota, that screened positive for mutations in MAPT and had a head MRI (n = 22). Voxel-based morphometry was used to assess patterns of gray matter atrophy in groups of subjects with the IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M mutations compared with age-and sex-matched controls. RESULTS: All MAPT groups showed gray matter loss in the anterior temporal lobes, with varying degrees of involvement of the frontal and parietal lobes. Within the temporal lobe, the subjects with IVS10+16, IVS10+3, N279K, and S305N mutations (mutations that influence the alternative splicing of tau pre-messenger RNA) all showed gray matter loss focused on the medial temporal lobes. In contrast to these groups, the subjects with P301L or V337M mutations (mutations that affect the structure of the tau protein) both showed gray matter loss focused on the lateral temporal lobes, with a relative sparing of the medial temporal lobe. CONCLUSION: There seem to be differences in patterns of temporal lobe atrophy across the MAPT mutations, which may aid in the differentiation of the different mutation carriers. Furthermore, there seems to be a possible association between mutation function and pattern of temporal lobe atrophy.

AB - OBJECTIVE: To use a case-control study to assess and compare patterns of gray matter loss across groups of subjects with different mutations in the microtubule-associated protein tau (MAPT) gene. METHODS: We identified all subjects from Mayo Clinic, Rochester, Minnesota, that screened positive for mutations in MAPT and had a head MRI (n = 22). Voxel-based morphometry was used to assess patterns of gray matter atrophy in groups of subjects with the IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M mutations compared with age-and sex-matched controls. RESULTS: All MAPT groups showed gray matter loss in the anterior temporal lobes, with varying degrees of involvement of the frontal and parietal lobes. Within the temporal lobe, the subjects with IVS10+16, IVS10+3, N279K, and S305N mutations (mutations that influence the alternative splicing of tau pre-messenger RNA) all showed gray matter loss focused on the medial temporal lobes. In contrast to these groups, the subjects with P301L or V337M mutations (mutations that affect the structure of the tau protein) both showed gray matter loss focused on the lateral temporal lobes, with a relative sparing of the medial temporal lobe. CONCLUSION: There seem to be differences in patterns of temporal lobe atrophy across the MAPT mutations, which may aid in the differentiation of the different mutation carriers. Furthermore, there seems to be a possible association between mutation function and pattern of temporal lobe atrophy.

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U2 - 10.1212/WNL.0b013e3181b9c8b9

DO - 10.1212/WNL.0b013e3181b9c8b9

M3 - Article

C2 - 19786698

AN - SCOPUS:70349693949

VL - 73

SP - 1058

EP - 1065

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 13

ER -