Researchers from the University of Cincinnati have provided evidence suggesting that it is the lessening of amyloid-beta in the brain that is behind cognitive decline and that boosting brain protein amounts may offer cognitive benefits. They found that most people with amyloid plaques do not develop Alzheimer’s disease, and those who remain cognitively normal have the ability to produce enough Aβ42, an important protein for brain health, to keep amyloid levels within a normal range. The study, published in the journal Brain, analyzed data from 26,000 people enrolled in 24 clinical trials for new monoclonal antibody treatments for Alzheimer’s.
The researchers focused on these new treatments, as they unintentionally increased levels of Aβ42 in the brain. Aβ42 reacts to various toxic and infectious exposures to defend the brain, transforming into amyloid plaques in the process. The study found that higher levels of Aβ42 after monoclonal antibody treatment were associated with slower cognitive impairment and clinical decline, independent of decreases in amyloid plaques. This finding suggests that Alzheimer’s is a process of loss of Aβ42 rather than a gain of amyloid, and future medications should aim to increase Aβ42 directly to combat cognitive decline.
Dr. David Merrill, a geriatric psychiatrist, noted that an increase in Aβ42 may explain the marginal benefits of the new drugs, but it is also important to consider modifiable risk factors for Alzheimer’s disease. Addressing factors such as exercise, diabetes, hypertension, and hearing loss may lower plaque loads in the brain while increasing soluble Aβ42 and improving cognitive function over time. More research is needed to elucidate the mechanisms of these modifiable risks and identify non-drug approaches that can provide similar benefits without the risks associated with new drugs.
Karen D. Sullivan, a neuropsychologist, emphasized that the findings of this study challenge the prevailing belief that Alzheimer’s is caused by the accumulation of amyloid-beta plaques. The study suggests that increased levels of amyloid-beta may actually result in less cognitive decline, contrary to traditional theories. The potential implications of this study may spark debates within the neuroscience community and prompt a reevaluation of current understandings of Alzheimer’s disease. It will be essential for future research to explore how increasing Aβ42 levels through various interventions can improve cognitive function and prevent cognitive decline in individuals at risk for Alzheimer’s.
