MRI correlates of neurofibrillary tangle pathology at autopsy: A voxel-based morphometry study

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Abstract

BACKGROUND: Neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau proteins, are one of the pathologic hallmarks of Alzheimer disease (AD). We aimed to determine whether patterns of gray matter atrophy from antemortem MRI correlate with Braak staging of NFT pathology. METHODS: Eighty-three subjects with Braak stage III through VI, a pathologic diagnosis of low- to high-probability AD, and MRI within 4 years of death were identified. Voxel-based morphometry assessed gray matter atrophy in each Braak stage compared with 20 pathologic control subjects (Braak stages 0 through II). RESULTS: In pairwise comparisons with Braak stages 0 through II, a graded response was observed across Braak stages V and VI, with more severe and widespread loss identified at Braak stage VI. No regions of loss were identified in Braak stage III or IV compared with Braak stages 0 through II. The lack of findings in Braak stages III and IV could be because Braak stage is based on the presence of any NFT pathology regardless of severity. Actual NFT burden may vary by Braak stage. Therefore, tau burden was assessed in subjects with Braak stages 0 through IV. Those with high tau burden showed greater gray matter loss in medial and lateral temporal lobes than those with low tau burden. CONCLUSIONS: Patterns of gray matter loss are associated with neurofibrillary tangle (NFT) pathology, specifically with NFT burden at Braak stages III and IV and with Braak stage itself at higher stages. This validates three-dimensional patterns of atrophy on MRI as an approximate in vivo surrogate indicator of the full brain topographic representation of the neurodegenerative aspect of Alzheimer disease pathology.

Original languageEnglish (US)
Pages (from-to)743-749
Number of pages7
JournalNeurology
Volume71
Issue number10
DOIs
StatePublished - Sep 2 2008

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Neurofibrillary Tangles
Autopsy
Pathology
Atrophy
Alzheimer Disease
tau Proteins
Temporal Lobe
Gray Matter
Brain

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

@article{1208cd3b20ef41a0a55930ab02cd739b,
title = "MRI correlates of neurofibrillary tangle pathology at autopsy: A voxel-based morphometry study",
abstract = "BACKGROUND: Neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau proteins, are one of the pathologic hallmarks of Alzheimer disease (AD). We aimed to determine whether patterns of gray matter atrophy from antemortem MRI correlate with Braak staging of NFT pathology. METHODS: Eighty-three subjects with Braak stage III through VI, a pathologic diagnosis of low- to high-probability AD, and MRI within 4 years of death were identified. Voxel-based morphometry assessed gray matter atrophy in each Braak stage compared with 20 pathologic control subjects (Braak stages 0 through II). RESULTS: In pairwise comparisons with Braak stages 0 through II, a graded response was observed across Braak stages V and VI, with more severe and widespread loss identified at Braak stage VI. No regions of loss were identified in Braak stage III or IV compared with Braak stages 0 through II. The lack of findings in Braak stages III and IV could be because Braak stage is based on the presence of any NFT pathology regardless of severity. Actual NFT burden may vary by Braak stage. Therefore, tau burden was assessed in subjects with Braak stages 0 through IV. Those with high tau burden showed greater gray matter loss in medial and lateral temporal lobes than those with low tau burden. CONCLUSIONS: Patterns of gray matter loss are associated with neurofibrillary tangle (NFT) pathology, specifically with NFT burden at Braak stages III and IV and with Braak stage itself at higher stages. This validates three-dimensional patterns of atrophy on MRI as an approximate in vivo surrogate indicator of the full brain topographic representation of the neurodegenerative aspect of Alzheimer disease pathology.",
author = "Whitwell, {Jennifer Lynn} and Josephs, {Keith Anthony} and Murray, {Melissa E} and Kantarci, {Kejal M} and Przybelski, {S. A.} and Weigand, {S. D.} and Vemuri, {Prashanthi D} and Senjem, {M. L.} and Parisi, {Joseph E} and Knopman, {David S} and Boeve, {Bradley F} and Petersen, {Ronald Carl} and Dickson, {Dennis W} and Jack, {Clifford R Jr.}",
year = "2008",
month = "9",
day = "2",
doi = "10.1212/01.wnl.0000324924.91351.7d",
language = "English (US)",
volume = "71",
pages = "743--749",
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TY - JOUR

T1 - MRI correlates of neurofibrillary tangle pathology at autopsy

T2 - A voxel-based morphometry study

AU - Whitwell, Jennifer Lynn

AU - Josephs, Keith Anthony

AU - Murray, Melissa E

AU - Kantarci, Kejal M

AU - Przybelski, S. A.

AU - Weigand, S. D.

AU - Vemuri, Prashanthi D

AU - Senjem, M. L.

AU - Parisi, Joseph E

AU - Knopman, David S

AU - Boeve, Bradley F

AU - Petersen, Ronald Carl

AU - Dickson, Dennis W

AU - Jack, Clifford R Jr.

PY - 2008/9/2

Y1 - 2008/9/2

N2 - BACKGROUND: Neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau proteins, are one of the pathologic hallmarks of Alzheimer disease (AD). We aimed to determine whether patterns of gray matter atrophy from antemortem MRI correlate with Braak staging of NFT pathology. METHODS: Eighty-three subjects with Braak stage III through VI, a pathologic diagnosis of low- to high-probability AD, and MRI within 4 years of death were identified. Voxel-based morphometry assessed gray matter atrophy in each Braak stage compared with 20 pathologic control subjects (Braak stages 0 through II). RESULTS: In pairwise comparisons with Braak stages 0 through II, a graded response was observed across Braak stages V and VI, with more severe and widespread loss identified at Braak stage VI. No regions of loss were identified in Braak stage III or IV compared with Braak stages 0 through II. The lack of findings in Braak stages III and IV could be because Braak stage is based on the presence of any NFT pathology regardless of severity. Actual NFT burden may vary by Braak stage. Therefore, tau burden was assessed in subjects with Braak stages 0 through IV. Those with high tau burden showed greater gray matter loss in medial and lateral temporal lobes than those with low tau burden. CONCLUSIONS: Patterns of gray matter loss are associated with neurofibrillary tangle (NFT) pathology, specifically with NFT burden at Braak stages III and IV and with Braak stage itself at higher stages. This validates three-dimensional patterns of atrophy on MRI as an approximate in vivo surrogate indicator of the full brain topographic representation of the neurodegenerative aspect of Alzheimer disease pathology.

AB - BACKGROUND: Neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau proteins, are one of the pathologic hallmarks of Alzheimer disease (AD). We aimed to determine whether patterns of gray matter atrophy from antemortem MRI correlate with Braak staging of NFT pathology. METHODS: Eighty-three subjects with Braak stage III through VI, a pathologic diagnosis of low- to high-probability AD, and MRI within 4 years of death were identified. Voxel-based morphometry assessed gray matter atrophy in each Braak stage compared with 20 pathologic control subjects (Braak stages 0 through II). RESULTS: In pairwise comparisons with Braak stages 0 through II, a graded response was observed across Braak stages V and VI, with more severe and widespread loss identified at Braak stage VI. No regions of loss were identified in Braak stage III or IV compared with Braak stages 0 through II. The lack of findings in Braak stages III and IV could be because Braak stage is based on the presence of any NFT pathology regardless of severity. Actual NFT burden may vary by Braak stage. Therefore, tau burden was assessed in subjects with Braak stages 0 through IV. Those with high tau burden showed greater gray matter loss in medial and lateral temporal lobes than those with low tau burden. CONCLUSIONS: Patterns of gray matter loss are associated with neurofibrillary tangle (NFT) pathology, specifically with NFT burden at Braak stages III and IV and with Braak stage itself at higher stages. This validates three-dimensional patterns of atrophy on MRI as an approximate in vivo surrogate indicator of the full brain topographic representation of the neurodegenerative aspect of Alzheimer disease pathology.

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U2 - 10.1212/01.wnl.0000324924.91351.7d

DO - 10.1212/01.wnl.0000324924.91351.7d

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C2 - 18765650

AN - SCOPUS:54049152421

VL - 71

SP - 743

EP - 749

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 10

ER -