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Nat Neurosci. 2018 Mar;21(3):424-431. doi: 10.1038/s41593-018-0070-z. Epub 2018 Feb 5.

Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals.

Author information

1
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA. hjacobs@mgh.harvard.edu.
2
The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA. hjacobs@mgh.harvard.edu.
3
Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, The Netherlands. hjacobs@mgh.harvard.edu.
4
The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
5
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
6
Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
7
Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.

Abstract

Animal models of Alzheimer's disease have suggested that tau pathology propagation, facilitated by amyloid pathology, may occur along connected pathways. To investigate these ideas in humans, we combined amyloid scans with longitudinal data on white matter connectivity, hippocampal volume, tau positron emission tomography and memory performance in 256 cognitively healthy older individuals. Lower baseline hippocampal volume was associated with increased mean diffusivity of the connecting hippocampal cingulum bundle (HCB). HCB diffusivity predicted tau accumulation in the downstream-connected posterior cingulate cortex in amyloid-positive but not in amyloid-negative individuals. Furthermore, HCB diffusivity predicted memory decline in amyloid-positive individuals with high posterior cingulate cortex tau binding. Our results provide in vivo evidence that higher amyloid pathology strengthens the association between HCB diffusivity and tau accumulation in the downstream posterior cingulate cortex and facilitates memory decline. This confirms amyloid's crucial role in potentiating neural vulnerability and memory decline marking the onset of preclinical Alzheimer's disease.

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