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Tau pathology mediates age effects on medial temporal lobe structure

Wisse, Laura EM LU ; Xie, Long ; Das, Sandhitsu R. ; de Flores, Robin ; Hansson, Oskar LU orcid ; Habes, Mohamad ; Doshi, Jimit ; Davatzikos, Christos ; Yushkevich, Paul A. and Wolk, David A. (2022) In Neurobiology of Aging 109. p.135-144
Abstract

Hippocampal atrophy is endemic in ‘normal aging’ but it is unclear what factors drive age-related changes in medial temporal lobe (MTL) structural measures. We investigated cross-sectional (n = 191) and longitudinal (n = 164) MTL atrophy patterns in cognitively normal older adults from ADNI-GO/2 with no to low cerebral β-amyloid and assessed whether white matter hyperintensities (WMHs) and cerebrospinal fluid (CSF) phospho tau (p-tau) levels can explain age-related changes in the MTL. Age was significantly associated with hippocampal volumes and Brodmann Area (BA) 35 thickness, regions affected early by neurofibrillary tangle pathology, in the cross-sectional analysis and with anterior and/or posterior hippocampus, entorhinal cortex and... (More)

Hippocampal atrophy is endemic in ‘normal aging’ but it is unclear what factors drive age-related changes in medial temporal lobe (MTL) structural measures. We investigated cross-sectional (n = 191) and longitudinal (n = 164) MTL atrophy patterns in cognitively normal older adults from ADNI-GO/2 with no to low cerebral β-amyloid and assessed whether white matter hyperintensities (WMHs) and cerebrospinal fluid (CSF) phospho tau (p-tau) levels can explain age-related changes in the MTL. Age was significantly associated with hippocampal volumes and Brodmann Area (BA) 35 thickness, regions affected early by neurofibrillary tangle pathology, in the cross-sectional analysis and with anterior and/or posterior hippocampus, entorhinal cortex and BA35 in the longitudinal analysis. CSF p-tau was significantly associated with hippocampal volumes and atrophy rates. Mediation analyses showed that CSF p-tau levels partially mediated age effects on hippocampal atrophy rates. No significant associations were observed for WMHs. These findings point toward a role of tau pathology, potentially reflecting Primary Age-Related Tauopathy, in age-related MTL structural changes and suggests a potential role for tau-targeted interventions in age-associated neurodegeneration and memory decline.

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author
; ; ; ; ; ; ; ; and
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aging, Longitudinal, Medial temporal lobe, Phospho-tau, Primary age-related tauopathy, White matter hyperintensities
in
Neurobiology of Aging
volume
109
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:85117960778
  • pmid:34740075
ISSN
0197-4580
DOI
10.1016/j.neurobiolaging.2021.09.017
language
English
LU publication?
yes
id
802fd269-16f9-462c-be31-5724abb7344e
date added to LUP
2021-11-22 15:40:23
date last changed
2022-11-16 18:49:10
@article{802fd269-16f9-462c-be31-5724abb7344e,
  abstract     = {{<p>Hippocampal atrophy is endemic in ‘normal aging’ but it is unclear what factors drive age-related changes in medial temporal lobe (MTL) structural measures. We investigated cross-sectional (n = 191) and longitudinal (n = 164) MTL atrophy patterns in cognitively normal older adults from ADNI-GO/2 with no to low cerebral β-amyloid and assessed whether white matter hyperintensities (WMHs) and cerebrospinal fluid (CSF) phospho tau (p-tau) levels can explain age-related changes in the MTL. Age was significantly associated with hippocampal volumes and Brodmann Area (BA) 35 thickness, regions affected early by neurofibrillary tangle pathology, in the cross-sectional analysis and with anterior and/or posterior hippocampus, entorhinal cortex and BA35 in the longitudinal analysis. CSF p-tau was significantly associated with hippocampal volumes and atrophy rates. Mediation analyses showed that CSF p-tau levels partially mediated age effects on hippocampal atrophy rates. No significant associations were observed for WMHs. These findings point toward a role of tau pathology, potentially reflecting Primary Age-Related Tauopathy, in age-related MTL structural changes and suggests a potential role for tau-targeted interventions in age-associated neurodegeneration and memory decline.</p>}},
  author       = {{Wisse, Laura EM and Xie, Long and Das, Sandhitsu R. and de Flores, Robin and Hansson, Oskar and Habes, Mohamad and Doshi, Jimit and Davatzikos, Christos and Yushkevich, Paul A. and Wolk, David A.}},
  issn         = {{0197-4580}},
  keywords     = {{Aging; Longitudinal; Medial temporal lobe; Phospho-tau; Primary age-related tauopathy; White matter hyperintensities}},
  language     = {{eng}},
  month        = {{01}},
  pages        = {{135--144}},
  publisher    = {{Elsevier}},
  series       = {{Neurobiology of Aging}},
  title        = {{Tau pathology mediates age effects on medial temporal lobe structure}},
  url          = {{http://dx.doi.org/10.1016/j.neurobiolaging.2021.09.017}},
  doi          = {{10.1016/j.neurobiolaging.2021.09.017}},
  volume       = {{109}},
  year         = {{2022}},
}