Researchers question prevailing Alzheimer's theory with new discovery: Scientists say restoring a brain protein, not removing amyloid plaques, should be the target of Alzheimer's dementia therapies

Experts believe that more than 6 million Americans have Alzheimer's dementia. A recent University of Cincinnati study sheds light on the condition and offers a controversial new treatment.In collaboration with the Karolinska institute in Sweden, the UC-led study suggests that normalizing levels of a particular brain protein, amyloid beta peptide, might be the key to treating Alzheimer's disease. This protein is essential in its original, soluble state to maintain brain health. However, sometimes, it can harden into amyloid plaques or "brain stones".This study appears in the journal EClinicalMedicine (published at the Lancet). It follows the FDA's conditional approval for aducanumab, a new medication that treats amyloid plaques.Alberto Espay is the senior author of the study and professor at UC neurology. "It's not plaques that are causing impaired cognitive function," he said. Espay, who is also a member the UC Gardner Neuroscience Institute, said that myloid plaques are a result, not a cause, of Alzheimer's disease.Alzheimer's disease was popularly known as the "long goodbye" in late 20th-century because of its slow decline in brain function and memory. However, it was more than 100 years ago that Alois Alzheimer, a scientist, first discovered plaques in patients with the disease.Espay claims that scientists have been working on ways to eradicate the plaques since then. He says that the UC team saw the matter differently. Cognitive impairment could result from a decrease in soluble amyloid beta peptide, rather than the corresponding accumulation. They analyzed brain scans and spinal fluid taken from 600 participants in the Alzheimer's Disease Neuroimaging Initiative. All of them had amyloid plaques. They then compared plaque levels and levels of the protein in cognitive impaired individuals to determine if they were normal. The cognitive functioning of individuals with high levels were found to be normal regardless of brain plaques.AdvertisementThe researchers also discovered that higher levels soluble amyloid beta peptide were associated to a larger hippocamp, which is the most critical area for memory.According to the authors, amyloid plaques are a common symptom of aging, but only a few people get dementia. They claim that by 85 years old, 60% of the population will have amyloid plaques. However, only 10% of those with dementia will develop them."The most important discovery of our analysis was that Alzheimer's symptoms seem dependent upon the depletion in the normal protein, which has a soluble form instead of when it aggregates to plaques," said Kariem Ezzat, co-author at the Karolinska Institute.Espay says that the best future treatment for Alzheimer's will be to restore brain soluble proteins back to their original levels.Now, the research team is working on animal models to validate their findings. Future treatments could be quite different than those that have been tried in the past two decades, if they are successful. Espay suggests that treatment may include increasing the soluble protein to keep the brain healthy and prevent the protein from hardening into plaques.Andrea Sturchio (University of Cincinnati) and Samir El Andaloussi (Karolinska Institute) are co-authors.The UC Gardner Neuroscience Institute funded the research.They disclose that REGAIN Therapeutics was founded by them recently. This patent application covers synthetic soluble, non-aggregating protein analogues for replacement therapy in proteinopathies.