Amyloid beta and tau proteins have long been linked to Alzheimer’s disease. The pathological accumulation of these proteins leads to cognitive decline in people with the disease. How it does this, however, remains poorly understood.
A new study from the labs of Sylvain Baillet of The Neuro and Sylvia Villeneuve of the Douglas Research Center provides important insight into how these proteins influence brain activity and may contribute to cognitive decline.
The team led by Jonathan Gallego Rudolf, a Ph.D. candidate in the Baillet and Villeneuve laboratories, recruited 104 people with a family history of Alzheimer’s disease. They scanned the participants’ brains using a combination of positron emission tomography (PET) to detect the presence and location of the proteins and magnetoencephalography (MEG) to record brain activity in these regions.
The scientists compared the results of the two scans and found that brain areas with elevated levels of amyloid-beta showed macroscopic manifestations of brain hyperactivity, reflected by increased fast- and decreased slow-frequency brain activity. In people with both amyloid beta and tau in their brains, the pattern shifted toward hypoactivity, with higher levels of pathology leading to a slowdown in brain activity.
Using cognitive tests, the team found that participants with higher rates of this amyloid-tau-related brain slowing showed higher rates of decline in attention and memory.
The findings suggest that the interplay between amyloid beta and tau leads to altered brain activity before noticeable cognitive symptoms appear. In a follow-up study, Rudolf plans to rescan the same participants over time to prove whether the accumulation of the two proteins promotes a further slowing of brain activity, and whether this accurately predicts the participants’ cognitive evolution.
Our study provides direct evidence in humans for the hypothesized shift in neurophysiological activity, from neural hyper- to hypo-activity, and its association with longitudinal cognitive decline. These results parallel findings from animal and computer models and contribute to advancing our understanding of the pathological mechanisms underlying the preclinical stage of Alzheimer’s disease.”
Jonathan Gallego Rudolf, Ph.D. candidate
Their findings were published in an article titled “Synergistic association of Aβ and tau pathology with cortical neurophysiology and cognitive decline in asymptomatic older adults” in the journal Nature Neuroscience on September 18, 2024.
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Magazine reference:
Gallego-Rudolf, J., et al. (2024). Synergistic association of Aβ and tau pathology with cortical neurophysiology and cognitive decline in asymptomatic older adults. Nature Neuroscience. doi.org/10.1038/s41593-024-01763-8.