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

• Published in: Nature neuroscience Vol. 21; no. 3; pp. 424 - 431
• Main Authors: Jacobs, Heidi I. L., Hedden, Trey, Schultz, Aaron P., Sepulcre, Jorge, Perea, Rodrigo D., Amariglio, Rebecca E., Papp, Kathryn V., Rentz, Dorene M., Sperling, Reisa A., Johnson, Keith A.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2018; Nature Publishing Group
• Subjects: 59/57; 59/78; 631/1647/245; 631/378/1689/1283; Accumulation; Aged; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid beta-protein; Animal Genetics and Genomics; Animal models; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Brain; Cingulum; Cognitive ability; Cortex (cingulate); Development and progression; Diffusivity; Female; Gyrus Cinguli - metabolism; Gyrus Cinguli - pathology; Health aspects; Healthy Volunteers; Hippocampus; Hippocampus - metabolism; Hippocampus - pathology; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Memory; Memory Disorders - metabolism; Memory Disorders - pathology; Memory Disorders - psychology; Neural Pathways - metabolism; Neurobiology; Neurosciences; Pathology; Positron emission; Positron emission tomography; Psychomotor Performance; Substantia alba; Tau protein; Tau proteins; tau Proteins - metabolism; Tomography; White Matter - metabolism; White Matter - pathology
• ISSN: 1097-6256; 1546-1726; 1546-1726
• DOI: 10.1038/s41593-018-0070-z

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. Using longitudinal multimodal imaging data collected in healthy older individuals, Jacobs et al. provide in vivo evidence in humans that amyloid deposition facilitates tau spread along connected pathways and memory decline.