Study Reveals Association between Aβ, Tau, Circuitry and Cognition


A new study published in Nature Neuroscience revealed an association between Aβ, Tau, Circuitry and Cognition. The study was conducted by Dr. Heidi Jacobs, instructor at MGH Gordon Center and a Marie Curie Fellow, and Dr. Keith Johnson, leader of the Aging NeuroImaging Program at the MGH Gordon Center, and the Harvard Aging Brain Study.

Using longitudinal multimodal imaging data collected in healthy older individuals, they provided in vivo evidence in humans that amyloid deposition facilitates tau spread along structurally connected pathways and this combination of events is associated with memory decline.

Imaging modalities included positron-emission tomography (PET) and magnetic resonance imaging (MRI). PET imaging was performed using the tracer flortaucipir (FTP), which binds to tau pathology, and the tracer Pittsburg compound-B (PiB), which indicates amyloid deposition. MR imaging was performed using T1-weighted images to measure hippocampal volume, and diffusion tensor imaging (DTI) was used to measure tract diffusivity.

The results of this study showed that hippocampal volume at baseline, a proxy for neurodegenerative processes including tau pathology, predict changes in diffusivity in a tract innervating the hippocampus, the hippocampal cingulum bundle (HCB), and not in a control tract, the uncinate fasciculus (UF).

These diffusivity changes in the hippocampal cingulum bundle were in turn associated with accumulation of tau pathology outside the medial temporal lobe, in the connected posterior cingulate cortex (PCC), in individuals with elevated levels of amyloid pathology. Finally, the combination of these diffusivity changes in the hippocampal cingulum bundle and higher levels of posterior cingulate cortex tau were associated with memory decline in individuals with elevated levels of amyloid pathology. These findings suggests that amyloid plays a crucial role in driving neurodegenerative processes and cognitive decline, and that monitoring spread of tau pathology will be important in clinical trials focused on removing amyloid plaques in the earliest stages of the diseases.

A detailed summary of this study is featured in AlzForum.

Associations between tract diffusivity, tau accumulation in the PCC, amyloid pathology and memory performance

Jacobs HI, Hedden T, Schultz AP, Sepulcre J, Perea RD, Amariglio RE, Papp KV, Rentz DM, Sperling RA, Johnson KA. "Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals" Nat Neurosci. 2018 Feb 5;

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