- Right now, the most widely accepted theory behind the cause of Alzheimer’s disease includes the build-up of amyloid-beta and tau proteins in the brain.
- Scientists are still not clear as to how these two proteins might cause Alzheimer’s disease.
- Researchers from McGill University found people with increased levels of both amyloid-beta and tau proteins in the brain may lead to changed brain activity before the cognitive symptoms of Alzheimer’s disease appear.
However, there are still questions on how amyloid plaques and tau tangles might cause this type of dementia.
“The role of amyloid-beta and tau proteins in Alzheimer’s disease has been well-established for decades,” Sylvain Baillet, PhD, professor of neurology and neurosurgery, and computer science and associate dean of research in the Faculty of Medicine & Health Sciences at McGill University in Canada explained to Medical News Today.
“While amyloid starts accumulating early in the aging brain, it alone isn’t enough to cause Alzheimer’s. The accumulation of tau comes later, and together, these proteins are present in the brains of Alzheimer’s patients. However, how the earliest deposits of both proteins affect brain activity in humans, especially before cognitive symptoms appear, wasn’t well understood,” he said.
Baillet is the senior author of a new study recently published in the journal Nature Neuroscience that offers new insight into this question.
The study found that increased levels of both amyloid-beta and tau proteins in the brain may lead to changed brain activity before the cognitive symptoms of Alzheimer’s disease appear.
For this study, researchers recruited 104 people who had a family history of Alzheimer’s disease. All study participants received positron emission tomography (PET) to look for any signs of the two proteins in the brain, as well as magnetoencephalography (MEG) to record brain activity in the areas where the proteins were present.
“Amyloid-beta and tau proteins are naturally found in the brain, but in Alzheimer’s disease, they both start to accumulate, possibly because brain activity is altered early in the disease and/or these accumulations modify brain activity, leading to a form of pathological chain reaction,” Baillet explained.
Amyloid-beta vs. tau proteins
“Amyloid-beta is a protein that can become sticky and form plaques between brain cells. These plaques block communication between cells and can cause inflammation, which damages the brain over time. Tau is a protein that usually helps support the internal structure of brain cells. In Alzheimer’s, tau proteins start to tangle inside the cells, disrupting their function and eventually leading to cell death.”
— Sylvain Baillet, PhD
At the study’s conclusion, Baillet and his team found that the brain areas within participants with increased levels of amyloid-beta show signs of brain hyperactivity.
However, those with higher levels of both amyloid-beta and tau proteins experienced hypoactivity or brain slowing. The researchers used cognitive tests and found hypoactivity study participants also had increased levels of attention and memory decline.
“We weren’t entirely surprised by this finding, but it was significant to observe it so clearly in humans,” Baillet said. “Animal models had predicted that amyloid-beta would accelerate brain activity, while the combination of amyloid-beta and tau would eventually lead to hypoactivity, or slowing of brain activity. However, this had not been directly observed in human subjects until now.”
“What was surprising was the extent to which this early slowing of brain activity in the presence of both proteins was predictive of later cognitive decline — three to four years after the MEG brain scans were collected. This connection between the early buildup of amyloid-beta and tau, changes in brain activity, and later memory and attention deficits highlights just how important it is to understand these proteins’ impact on the brain, and how brain activity may alter in a subtle fashion, long before symptoms appear.”
— Sylvain Baillet, PhD
Baillet said their next research steps involve continuing to follow the same participants over nearly 10 years, with follow-up MEG scans, amyloid, and tau PET imaging, and detailed cognitive testing currently being performed.
“Using these unique datasets from the PREVENT-AD cohort, we aim to refine how well we can predict cognitive decline and Alzheimer’s symptoms from short MEG scans, potentially up to a decade before they emerge,” he continued. “I want to emphasize that these PREVENT-AD datasets will be released to all researchers, for replication and encouraging novel findings.”
MNT also spoke with Clifford Segil, DO, neurologist at Providence Saint John’s Health Center in Santa Monica, CA, about this study.
“This is a creative study which leaves me asking how the authors determined that its participants would have long-term cognitive declines as the data I reviewed noted its participants scored on average a 28.1 out of 30 on a Montreal Cognitive Assessment (MoCa) score and then a 28.8 on MMSE (mini-mental state examination) score during MEG-PE, but there is no data to support these patients would have cognitive decline,” Segil said.
“When I reviewed this paper, I (was) left confused how the authors determined that its participants would have ‘longitudinal declines’ or worsening memory loss as the belief that brain amyloid and tau levels always cause cognitive issues remains controversial,” he continued.
“Many clinical neurologists like me remain unconvinced that the build of any brain proteins is pathological and leads to cognitive decline. As the clinical use of anti-amyloid medications in practice continues to not provide any meaningful or observational changes in mental status, cognitive abilities or anything noticeable in patients receiving anti-brain amyloid medications, researchers position that amyloid and tau proteins caused memory loss is becoming more unbelievable,” he added.
Segil said he would like to see follow-up cognitive testing done to determine if patients with high brain amyloid or tau have poor cognition, as practicing neurologists continue to believe that brain amyloid is not directly proportional to cognitive burden.
“The clinical use of anti-brain amyloid medications [in] the United States is demonstrating that the patients receiving these anti-amyloid medications are without any noticeable changes in [cognition], supporting clinician’s positions that brain amyloid and tau are less likely to be toxic or cause dementia’s cognitive symptoms.”
— Clifford Segil, DO
