The UC-led study, performed in partnership with the Karolinska Institute in Sweden, claims that the treatment of Alzheimers disease might lie in stabilizing the levels of a particular brain protein called amyloid-beta peptide. This protein is needed in its initial, soluble form to keep the brain healthy, however often it solidifies into “brain stones” or clumps, called amyloid plaques.
The research study, which appears in the journal EClinicalMedicine (published by the Lancet), comes on the heels of the FDAs conditional approval of a new medication, aducanumab, that treats the amyloid plaques.
Study results graphic. Credit: Life Science Animation
” Its not the plaques that are triggering impaired cognition,” says Alberto Espay, the brand-new studys senior author and teacher of neurology at UC. “Amyloid plaques are a repercussion, not a cause,” of Alzheimers illness, says Espay, who is also a member of the UC Gardner Neuroscience Institute.
Alzheimers disease ended up being widely referred to as “the long bye-bye” in the late 20th century due to the diseases slow degeneration of brain function and memory. It was over 100 years earlier, however, that researcher Alois Alzheimer initially determined plaques in the brain of patients struggling with the illness.
Considering that then, Espay states that scientists have concentrated on treatments to remove the plaques. However the UC team, he says, saw it differently: Cognitive disability might be due to a decline in soluble amyloid-beta peptide rather of the corresponding accumulation of amyloid plaques. To test their hypothesis, they examined the brain scans and back fluid from 600 individuals enrolled in the Alzheimers Disease Neuroimaging Initiative study, who all had amyloid plaques. From there, they compared the quantity of plaques and levels of the peptide in the people with typical cognition to those with cognitive impairment. They found that, despite the quantity of plaques in the brain, the people with high levels of the peptide were cognitively normal.
Alberto Espay, MD, MSc, 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 Parkinsons Disease and Movement Disorders. Credit: Colleen Kelley/UC Brand + Creative
They likewise discovered that greater levels of soluble amyloid-beta peptide were connected with a bigger hippocampus, the area of the brain most crucial for memory.
According to the authors, as we age many people establish amyloid plagues, however couple of individuals develop dementia. In fact, by the age of 85, 60% of individuals will have these plagues, however just 10% develop dementia, they state.
” The crucial discovery from our analysis is that Alzheimers disease symptoms appear based on the depletion of the typical protein, which remains in a soluble state, instead of when it aggregates into plaques,” states co-author Kariem Ezzat from the Karolinska Institute.
The most relevant future therapeutic approach for the Alzheimers program will be renewing these brain soluble proteins to their typical levels, says Espay.
The research study group is now working to evaluate their findings in animal models. If successful, future treatments might be very different from those attempted over the last 2 years. Treatment, states Espay, might consist of increasing the soluble version of the protein in a way that keeps the brain healthy while avoiding the protein from hardening into plaques.
Referral: 28 June 2021, EClinicalMedicine.DOI: 10.1016/ j.eclinm.2021.100988.
Co-authors include: Andrea Sturchio, University of Cincinnati, and Samir EL Andaloussi, Karolinska Institute.
The research was funded by the UC Gardner Neuroscience Institute.
The authors reveal that they have just recently cofounded REGAIN Therapeutics, owner of a patent application that covers synthetic soluble non-aggregating peptide analogues as replacement treatment in proteinopathies.
Because then, Espay states that researchers have focused on treatments to remove the plaques. The UC group, he says, saw it in a different way: Cognitive impairment might be due to a decline in soluble amyloid-beta peptide rather of the matching accumulation of amyloid plaques. To test their hypothesis, they examined the brain scans and spinal fluid from 600 individuals enrolled in the Alzheimers Disease Neuroimaging Initiative study, who all had amyloid plaques. They discovered that, regardless of the amount of plaques in the brain, the people with high levels of the peptide were cognitively regular.
Treatment, says Espay, might consist of increasing the soluble version of the protein in a manner that keeps the brain healthy while preventing the protein from hardening into plaques.
Researchers at University of Cincinnati state bring back a brain protein, not removing amyloid plaques, need to be the target of Alzheimers dementia therapies.
Professionals estimate more than 6 million Americans are living with Alzheimers dementia. A recent study, led by the University of Cincinnati, sheds new light on the disease and a highly disputed new drug treatment.