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Tau pathology mediates age effects on medial temporal lobe structure

Year: 2021
Type: article
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 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.
DOI: 10.1016/j.neurobiolaging.2021.09.017
Authors: 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
Institutions: Lund University, University of Pennsylvania, Inserm, Université de Caen Normandie, Skåne University Hospital, The University of Texas at San Antonio Health Science Center
Language: English
Field: Medicine
Open Access status: hybrid
Estimated APC paid: $3,200
Funders: Alzheimer's Association, BrightFocus Foundation, University of Pennsylvania, National Institutes of Health, National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering
Awards: G104586243, G1310852075, G1635571750, G2957681590, G343469054, G36433118, G3718875363, G3919444319, G4257815260, Adaptive Large-Scale Framework for Automatic Biomedical Image Segmentation, G504619356, Alzheimer's Disease Neuroimaging Initiative, Biomedical Image Computing and Informatics Cluster, Modulators of Medial Temporal Lobe Subregion Structure and Function in Normal and Pathological Aging, G856368605, G9000008846, G9000033698, G9000054871, G9000057963, G9000091466, G9000144445, Alzheimer's Disease Neuroimaging Initiative (ADNI4), Penn Alzheimer's Disease Research Center (ADRC), Ultrascale Machine Learning to Empower Discovery in Alzheimers Disease Biobanks, Etiology and Progression of Suspected Non-Alzheimer’s Pathophysiology
OpenAlex ID: W3204562224
FWCI: 2.052
Cites: 85
Cited by: 24
Related to: 10