The accumulation of the protein amyloid-beta in the brain is one of the primary theories explaining Alzheimer’s. Evidence from University of Cincinnati researchers points to the reduction of amyloid-beta in the brain as the cause of cognitive decline. Researchers believe increasing brain protein levels could improve cognition.
While scientists still don’t know the exact cause of Alzheimer’s, current theories involve the accumulation of a protein called amyloid-beta in the brain.
Researchers at the University of Cincinnati now have evidence that suggests cognitive loss is caused by a decrease in amyloid-beta in the brain, and increasing brain protein levels may improve cognitive function.
According to the study published in the journal Brain, increases in protein levels associated with new Alzheimer’s medicines may explain both the slowing of cognitive impairment and the reduction in amyloid plaques [1].
The loss of Aβ42 contributes to Alzheimer’s.
Alberto Espay, MD, the lead author and professor of neurology at the UC College of Medicine and director and endowed chair of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders at the UC Gardner Neuroscience Institute at the University of Cincinnati, and his team discovered that the majority of people with amyloid plaques do not develop Alzheimer’s.
According to Espay, only one-fifth of people with amyloid plaques go on to develop Alzheimer’s by the time they are 85. They found that the ability to create enough Aβ42, a crucial protein for brain health, to maintain those levels within a normal range is what keeps people with amyloid plaques cognitively normal, not the amount of plaques in the brain.
For decades, the accepted consensus in the field has been that a 42-amino-acid protein called amyloid-beta 42 (Aβ42) accumulates into clumps called amyloid plaques, which damage the brain and cause Alzheimer’s.
Espay and teams hypothesized that normal, soluble Aβ42 in the brain is necessary for cell health and that loss of Aβ42, not plaque accumulation, contributes to Alzheimer’s. There is published evidence that indicates dementia develops when Aβ42 levels are very low rather than when plaque levels are high [3].
The brain’s typical reaction to biological, infectious, or metabolic stress seems to be the conversion of Aβ42 into plaques, according to Espay’s findings.
Focusing on monoclonal antibody therapies.
For this study, researchers examined data from over 26,000 participants in 24 randomized clinical trials for newly approved Alzheimer’s treatments using monoclonal antibodies [3]. They assess cognitive impairment and differences Aβ42 levels before and after treatment.
After observing that these novel medicines inadvertently raised Aβ42 levels in the brain, Espay and his colleagues decided to concentrate on them.
According to Espay, Aβ42 is a protein that responds to various infectious and toxic exposures to protect the brain. During that process, Aβ42 stops working and changes into amyloid plaques. One could think of the plaques as Aβ42’s tombstones.
He added that they were interested in discovering whether any cognitive advantages may be explained by the rise in Aβ42 as much as by the decline in amyloid plaques. The data was available for extraction from each monoclonal antibody trial report’s supplemental material.
Higher levels of amyloid-beta are associated with slower cognitive deterioration.
Researchers analyzed the study data and found that slower cognitive impairment and clinical decline were independently linked to greater levels of Aβ42 following monoclonal antibody treatment.
The same group’s previous research has already demonstrated that, regardless of the levels of amyloid plaques, normal cognition is linked to cerebrospinal fluid Aβ42 levels above a particular threshold of compensation [2]. Higher baseline Aβ42 levels predict a slower progression to dementia, even in people with genetic types of Alzheimer’s.
Espay said that Alzheimer’s is a result of Aβ42 loss rather than amyloid buildup. Regardless of how many plaques there are, the brain does not swell but continues undergoing atrophy. Future treatments should directly increase Aβ42 rather than indirectly, as the current antibodies do.
Researchers are investigating treatments that could boost Aβ42 levels as a type of rescue treatment.
Alzheimer’s Research Association is a non-profit organization dedicated to helping caregivers of Alzheimer’s disease and dementia. We provide the latest information and news about the illness and helpful tips to help caregivers cope with their daily caregiving challenges. We realize the most important thing that a caregiver needs is financial assistance. Therefore, we provide grants to caregivers to ease their financial burden. Caregivers can apply for grants here: Alzheimer’s Grant Application.
You can also help caregivers in their endeavor by donating as much as possible: Donation To Alzheimer’s Research Associations.
References
- Abanto, J., Dwivedi, A.K., Imbimbo, B.P. and Espay, A.J., 2024. Increases in amyloid-β42 slow cognitive and clinical decline in Alzheimer’s disease trials. Brain, 147(10), pp.3513-3521.
- Sturchio, A., Dwivedi, A.K., Malm, T., Wood, M.J., Cilia, R., Sharma, J.S., Hill, E.J., Schneider, L.S., Graff-Radford, N.R., Mori, H. and Nübling, G., 2022. High soluble amyloid-β42 predicts normal cognition in amyloid-positive individuals with Alzheimer’s disease-causing mutations. Journal of Alzheimer’s Disease, 90(1), pp.333-348.
- Cummings, J., Osse, A.M.L., Cammann, D., Powell, J. and Chen, J., 2024. Anti-amyloid monoclonal antibodies for the treatment of Alzheimer’s disease. BioDrugs, 38(1), pp.5-22.
- New study challenges amyloid-beta theory on cause for Alzheimer’s disease. Medical News Today. https://www.medicalnewstoday.com/articles/brain-protein-challenges-amyloid-beta-theory-cause-alzheimers-disease. Published Online: 18th September, 2024. Accessed: 14th October, 2024.
- Boosting brain protein levels may slow decline from Alzheimer’s. Science Daily. https://www.sciencedaily.com/releases/2024/09/240911112040.htm. Published Online: 11th September, 2024. Accessed: 15th October, 2024.
- Alzheimer’s decline may be slowed by protein boost. UC News. https://www.uc.edu/news/articles/2024/09/alzheimers-decline-may-be-slowed-by-protein-boost.html. Published Online: 12th September, 2024. Accessed: 15th October, 2024.