Study finds two proteins impact brain activity differently

Beta-amyloid and tau proteins have long been associated with Alzheimer’s disease. Pathological accumulation of these proteins leads to cognitive decline in people with the disease. However, it is not clear exactly how this happens.

A new study from the labs of Sylvain Baillet at The Neuro and Sylvia Villeneuve at the Douglas Research Centre provides important insights into how these proteins influence brain activity and may contribute to cognitive decline. Their findings were published in an article titled “Synergistic association of Aβ and tau pathology with cortical neurophysiology and cognitive falliculitis in asymptomatic older adults” in the journal Neuroscience of Nature September 18, 2024.

The team led by Jonathan Gallego Rudolf, a PhD student in Baillet and Villeneuve’s labs, 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 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 increased levels of beta-amyloid showed macroscopic expressions of brain hyperactivity, reflected by increased fast-frequency brain activity and decreased slow-frequency brain activity. In people with both beta-amyloid and tau in their brains, the pattern shifted toward hypoactivity, with higher levels of pathology leading to slower brain activity.

Using cognitive tests, the team found that participants with higher levels of this amyloid-tau-related brain slowing had higher levels of attention and memory decline.

The results suggest that the interaction between beta-amyloid and tau leads to impaired brain activity before noticeable cognitive symptoms appear. In a follow-up study, Rudolf plans to re-examine the same participants over time to prove whether the accumulation of both proteins promotes further slowing of brain activity and whether this accurately predicts the participants’ cognitive outcomes.

“Our study provides direct evidence in humans of the hypothesized shift in neurophysiological activity from neuronal hyperactivity to hypoactivity and its association with longitudinal cognitive decline. These findings are consistent with those from animal and computational models and contribute to advancing our understanding of the pathological mechanisms underlying preclinical Alzheimer’s disease,” says Rudolf.