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New discovery in how Alzheimer’s disease spreads through the brain

June 14, 2024

New research has uncovered how a toxic protein known to contribute to Alzheimer’s disease development, spreads through the brain; offering new avenues for targeted treatment.

“We found that one of the two key toxic species in the development and progression of Alzheimer’s disease – tau tangles – do not accumulate randomly in the brain; instead, they follow specific patterns of brain connectivity, and in stages,” says Dr. Maged Goubran, senior author of the study and a scientist in the Physical Sciences Platform and Hurvitz Brain Sciences Program at Sunnybrook Research Institute (SRI).

“These findings suggest that tau uses the brain’s network architecture to fuel its accumulation, providing researchers with a novel – and potentially more effective – approach to develop targeted treatments for patients with, or at risk of, Alzheimer’s disease.”

Tau tangles, along with amyloid plaques, and the associated neuroinflammation with these two toxic species in the brain, are the key players that lead to cognitive decline and the development and progression of Alzheimer’s disease. Earlier studies suggested that synaptic connections between neurons are key pathways for the spreading of tau.

The new study, published in Nature Communications, unveils that the different brain networks progressively affected by Alzheimer's disease pathology may be largely determined by underlying large-scale patterns of brain organization, the so-called ‘gradients of connectivity’.

These gradients of connectivity represent large-scale patterns of how the different brain regions communicate with each other. The researchers found that these connectivity gradients contract, which likely represents de-specialization of specific functional networks. This network de-specialization was associated with cognitive decline in regions with high tau, demonstrating a detrimental interaction between network reorganization and tau on cognition.

“We found that specific brain hubs, which are highly connected regions and tau epi-centers, can predict where tau will build up next,” says the study’s first author Dr. Julie Ottoy, a research associate at SRI and lecturer at the University of Toronto. “Notably, such an approach could lead to more personalized treatment strategies tailored to the unique brain network architecture of each patient. This means that targeting these hubs with brain stimulation might be one avenue to slow down the disease more effectively.”

This research was conducted in collaboration with Dr. Pedro Rosa-Neto at McGill University, and was funded by the Canadian Institutes for Health Research, the Alzheimer’s Association, and the Alzheimer’s Society of Canada. Dr. Ottoy was funded by a prestigious Alzheimer’s Association Research Fellowship (AARF) during the study under the supervision of Dr. Goubran and Dr. Sandra Black at SRI.