Researchers Map How Alzheimer’s Pathology Spreads Across Brain Networks

Capitalizing on recent advances in neuroimaging and genetic biomarker research, scientists have been able to identify specific pathways by which tau and beta-amyloid, two proteins that are hallmarks of Alzheimer’s disease, accumulate in the brain over time. Researchers also found the patterns of tau and beta-amyloid accumulation were related to specific genetic profiles, providing better understanding of Alzheimer’s disease risk and possible new avenues for diagnosis and monitoring of the disease.

Improved technology makes possible for intensive, side-by-side comparisons of how tau and beta-amyloid spread in the brain in distinctive patterns. Using this technology, researchers were able to reveal nuances into how, even in disease, the brain follows a dynamic and complex network of circuits and connections.

In a brain with Alzheimer’s disease, abnormal deposits of tau and beta-amyloid do not randomly appear, but instead show unique spatial patterns that follow the brain’s existing connected neural networks. To better understand how tau and beta-amyloid interact with and influence each other, the researchers looked closely at 3-D brain network and gene maps and found that both tau and beta-amyloid were associated with genes devoted to lipid metabolism, and that the APOE E4 gene – a risk factor for Alzheimer’s disease – played a central role in the relationships of these genetic networks.

The scientists found common genetic background for the malfunction of both proteins. The findings showed that in addition to APOE, other variations in genetic pathways shared by tau and beta-amyloid could trigger their accumulation. The study also found that tau propagation was associated with an axon-related (parts of neurons that pass messages away from the cell body) genetic profile, while beta-amyloid’s spread was connected with a dendrite-related (parts of neurons that receive messages from other cells) genetic profile.

The researchers hope this new understanding of tau and beta-amyloid’s propagation patterns can be combined with a person’s genetic profile to help develop precision medicine approaches for improved diagnosis, monitoring, and therapies for Alzheimer’s disease in the brain.

For details, see Sepulcre. J. et al. (2018). Neurogenetic contributions to amyloid beta and tau spreading in the human cortex. Nature Medicine. doi:10.1038/s41591-018-0206-4. [Epub ahead of print]