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Greater tau load and reduced cortical thickness in APOE ε4-negative Alzheimer’s disease : a cohort study

Mattsson, Niklas LU ; Ossenkoppele, Rik LU ; Smith, Ruben LU ; Strandberg, Olof LU ; Ohlsson, Tomas; Jögi, Jonas LU ; Palmqvist, Sebastian LU ; Stomrud, Erik LU and Hansson, Oskar LU (2018) In Alzheimer's Research and Therapy 10(1).
Abstract

Background: Alzheimer’s disease is characterized by aggregated β-amyloid and tau proteins, but the clinical presentations and patterns of brain atrophy vary substantially. A part of this heterogeneity may be linked to the risk allele APOE ε4. The spread of tau pathology is related to atrophy and cognitive decline, but little data exist on the effects of APOE ε4 on tau. The objective of this preliminary study was therefore to test if tau load and brain structure differ by APOE ε4 in Alzheimer’s disease. Methods: Sixty-five β-amyloid-positive patients at the prodromal and dementia stages of Alzheimer’s disease were enrolled, including APOE ε4-positive (n = 46) and APOE ε4-negative (n = 19) patients. 18F-AV-1451 positron emission... (More)

Background: Alzheimer’s disease is characterized by aggregated β-amyloid and tau proteins, but the clinical presentations and patterns of brain atrophy vary substantially. A part of this heterogeneity may be linked to the risk allele APOE ε4. The spread of tau pathology is related to atrophy and cognitive decline, but little data exist on the effects of APOE ε4 on tau. The objective of this preliminary study was therefore to test if tau load and brain structure differ by APOE ε4 in Alzheimer’s disease. Methods: Sixty-five β-amyloid-positive patients at the prodromal and dementia stages of Alzheimer’s disease were enrolled, including APOE ε4-positive (n = 46) and APOE ε4-negative (n = 19) patients. 18F-AV-1451 positron emission tomography was used to measure tau and brain magnetic resonance imaging (MRI) was used to measure cortical thickness. Results: Compared with their APOE ε4-positive counterparts, APOE ε4-negative patients had greater tau load and reduced cortical thickness, with the most pronounced effects for both in the parietal cortex. Relative to the overall cortical tau load, APOE ε4-positive patients had greater tau load in the entorhinal cortex. APOE ε4-positive patients also had slightly greater cortical β-amyloid load. There was an interaction between APOE ε4 and 18F-AV-1451 on cortical thickness, with greater effects of 18F-AV-1451 on cortical thickness in APOE ε4-negative patients. APOE ε4 and 18F-AV-1451 were independent predictors of cognition, but showed distinct associations with different cognitive tests. Conclusions: APOE genotype may be associated with differences in pathways in Alzheimer’s disease, potentially through differential development and spread of tau, as well as through effects on cognitive outcomes involving non-tau-related mechanisms.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, APOE, Atrophy, Cognition, Tau
in
Alzheimer's Research and Therapy
volume
10
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85051185770
ISSN
1758-9193
DOI
10.1186/s13195-018-0403-x
language
English
LU publication?
yes
id
acbaf4d8-2401-4a9d-afe3-c4a1368c80ec
date added to LUP
2018-09-10 13:06:50
date last changed
2019-01-06 14:04:07
@article{acbaf4d8-2401-4a9d-afe3-c4a1368c80ec,
  abstract     = {<p>Background: Alzheimer’s disease is characterized by aggregated β-amyloid and tau proteins, but the clinical presentations and patterns of brain atrophy vary substantially. A part of this heterogeneity may be linked to the risk allele APOE ε4. The spread of tau pathology is related to atrophy and cognitive decline, but little data exist on the effects of APOE ε4 on tau. The objective of this preliminary study was therefore to test if tau load and brain structure differ by APOE ε4 in Alzheimer’s disease. Methods: Sixty-five β-amyloid-positive patients at the prodromal and dementia stages of Alzheimer’s disease were enrolled, including APOE ε4-positive (n = 46) and APOE ε4-negative (n = 19) patients. 18F-AV-1451 positron emission tomography was used to measure tau and brain magnetic resonance imaging (MRI) was used to measure cortical thickness. Results: Compared with their APOE ε4-positive counterparts, APOE ε4-negative patients had greater tau load and reduced cortical thickness, with the most pronounced effects for both in the parietal cortex. Relative to the overall cortical tau load, APOE ε4-positive patients had greater tau load in the entorhinal cortex. APOE ε4-positive patients also had slightly greater cortical β-amyloid load. There was an interaction between APOE ε4 and 18F-AV-1451 on cortical thickness, with greater effects of 18F-AV-1451 on cortical thickness in APOE ε4-negative patients. APOE ε4 and 18F-AV-1451 were independent predictors of cognition, but showed distinct associations with different cognitive tests. Conclusions: APOE genotype may be associated with differences in pathways in Alzheimer’s disease, potentially through differential development and spread of tau, as well as through effects on cognitive outcomes involving non-tau-related mechanisms.</p>},
  articleno    = {45},
  author       = {Mattsson, Niklas and Ossenkoppele, Rik and Smith, Ruben and Strandberg, Olof and Ohlsson, Tomas and Jögi, Jonas and Palmqvist, Sebastian and Stomrud, Erik and Hansson, Oskar},
  issn         = {1758-9193},
  keyword      = {Alzheimer’s disease,APOE,Atrophy,Cognition,Tau},
  language     = {eng},
  month        = {08},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Alzheimer's Research and Therapy},
  title        = {Greater tau load and reduced cortical thickness in APOE ε4-negative Alzheimer’s disease : a cohort study},
  url          = {http://dx.doi.org/10.1186/s13195-018-0403-x},
  volume       = {10},
  year         = {2018},
}