Tau pathology mediates age effects on medial temporal lobe structure

Laura EM Wisse, Long Xie, Sandhitsu R. Das, Robin de Flores, Oskar Hansson, Mohamad Habes, Jimit Doshi, Christos Davatzikos, Paul A. Yushkevich, David A. Wolk, Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)135-144
Number of pages10
JournalNeurobiology of Aging
Publication statusPublished - 2022 Jan 1

Subject classification (UKÄ)

  • Neurosciences

Free keywords

  • Aging
  • Longitudinal
  • Medial temporal lobe
  • Phospho-tau
  • Primary age-related tauopathy
  • White matter hyperintensities


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