Alzheimer’s: Study suggests alternative to amyloid plaque theory

Amyloid plaques have long been recognized as the main cause of symptoms in Alzheimer’s disease and a target for therapies.

Earlier this year, however, Dr. Matthew Schrag, assistant professor of neurology and director of the Cerebral Amyloid Angiopathy Clinic at Vanderbilt University, states that an influential and widely cited Study 2006 This led many researchers to study amyloid plaques, which may have distorted images.

In the current study, the researchers built on findings from their previous research that people with high levels of soluble amyloid beta were cognitively normal even when they had amyloid plaques.

Those with lower levels of soluble amyloid beta were more likely to show cognitive impairment.

The researchers hypothesized that it was not the accumulation of insoluble amyloid plaques, but the concomitant decrease in soluble amyloid beta that caused the symptoms.

The study looked at people participating in the Dominantly Inherited Alzheimer Network (DIAN) cohort study. These people have mutations that make them more likely to develop amyloid plaques in the brain, which are thought to increase their chances of developing Alzheimer’s disease.

dr Anton Porsteinsson, professor and director of the Alzheimer’s Disease Care, Research and Education Program (AD-CARE) at the University of Rochester Medical Center, who is part of the DIAN consortia but not an author on the study, said Medical news today:

“This is a very unique group of participants. All have a dominant inheritance of Alzheimer’s disease, which is a decidedly small subgroup. They may differ in some ways from the much more common sporadic AD group. The DIAN cohort study is very well designed and thought out.”

Researchers performed clinical assessments of cognitive function on all participants using the Dementia Clinical Rating Scale. You also measured [beta-amyloid-42], p-tauand t-tau levels in their cerebrospinal fluid (CSF) and used neuroimaging to quantify insoluble brain plaques.

Participants were tested at baseline and after a median follow-up of 3.3 years (range 1-9 years).

Participants with higher levels of soluble amyloid beta were less likely to show cognitive decline even if they had amyloid plaques. Lower levels of soluble amyloid beta were strongly associated with more rapid cognitive decline.

dr Porsteinsson commented, “Here we have DIAN participants who were positive on an amyloid PET scan, meaning they have an elevated amyloid plaque burden. You would expect your soluble CSF and plasma [beta-amyloid-42] be low as the plaques absorb them from the soluble form.”

“Here,” he added, “those that are more soluble [beta-amyloid-42] seem to work better than those that are lower [beta-amyloid-42] in terms of disease stability. Perhaps they have a milder or lower stage of the disease oligomeric amyloid form load.”

In the study, those with a baseline level of soluble amyloid beta in the brain greater than 270 picograms per milliliter remained cognitively normal, regardless of the amount of amyloid plaques in their brain.

“What’s new here in my book is the soluble [beta-amyloid-42] Concentrations and plaque load don’t go hand in hand and that’s a drop soluble [beta-amyloid-42] is a stronger predictor of poor clinical outcome than plaque burden.”

– dr Anton Porsteinsson

Lead author Prof Alberto Espay commented: “If you break away from the prejudices that we have created for too long, it makes only too logical that a neurodegenerative process is caused by something we are losing, amyloid-beta, and not by something that we win, amyloid plaques.”

“Degeneration is a loss process and what we lose turns out to be much more important,” he added.

The authors are now investigating whether therapies that increase levels of soluble amyloid beta might be effective in fighting Alzheimer’s disease.

“The possibility that higher concentrations are soluble [beta-amyloid-42] is therapeutic and promoting soluble [beta-amyloid-42] could be therapeutic is really fascinating.”

– dr Anton Porsteinsson

The researchers suspect that a similar mechanism could be at work in Parkinson’s disease. Insoluble deposits in the brain called Lewy bodies are thought to cause many of the symptoms.

However, the researchers hypothesize that a decrease in the level of normal, soluble alpha-synuclein rather than its formation into insoluble Lewy bodies is responsible.

However, some experts noted that the results of this small sample, all of which carry a rare gene that predisposes them to Alzheimer’s disease, should be treated with caution.

dr Rebecca Edelmayer, senior director of scientific engagement for the Alzheimer’s Association, said MNT the “[b]Being able to detect and measure brain changes associated with Alzheimer’s and accurately predict progression to cognitive decline is incredibly important both clinically and research.”

She continued, “This newspaper finds this CSF [beta-amyloid-42] It is already known that levels can be predictive of amyloid levels in the brain. However, the conclusion that high concentrations of CSF [beta-amyloid-42] [are] a better predictor of protection from cognitive decline, even in individuals who already have amyloid plaque, may be an overstatement based on the samples analyzed and does not prove a new hypothesis or disprove an existing hypothesis.”

Thus, although this study opens new areas of investigation in the search for effective therapies, it does not yet provide a panacea for Alzheimer’s disease and other neurodegenerative diseases.