Study: Decreased proteins, not amyloid plaques, tied to Alzheimer's disease - EurekAlert

The protein normally carries out its functions in the brain in a form that is soluble, meaning dissolvable in water, but it sometimes hardens into clumps, known as amyloid plaques.

But Espay and his colleagues hypothesized that plaques are simply a consequence of the levels of soluble amyloid-beta in the brain decreasing.

Sturchio noted that many research studies and clinical trials over the years have aimed at reducing amyloid plaques in the brain, and some have lessened plaques, but until the September 27 announcement of a positive trial by Biogen and Eisai (lecanemab), none slowed the progression of  Alzheimer’s disease.

Previous research from the team found that regardless of the buildup of plaques in the brain, people with high levels of soluble amyloid-beta were cognitively normal, while those with low levels of the protein were more likely to have cognitive impairment.

In the current study, the team analyzed the levels of amyloid-beta in a subset of patients with mutations that predict an overexpression of amyloid plaques in the brain, which is thought to make them more likely to develop Alzheimer’s disease.

“What we found was that individuals already accumulating plaques in their brains who are able to generate high levels of soluble amyloid-beta have a lower risk of evolving into dementia over a three-year span,” Espay said.

The research found that with a baseline level of soluble amyloid-beta in the brain above 270 picograms per milliliter, people can remain cognitively normal regardless of the amount of amyloid plaques in their brains.

Sturchio said the research is moving forward to study if increasing the levels of soluble amyloid-beta in the brain is a beneficial therapy for patients with Alzheimer’s. .

Espay said it will be important to ensure that the elevated levels of the protein introduced into the brain do not then turn into amyloid plaques, since the soluble version of the protein is needed for normal function to make an impact in the brain. !

For example, in Parkinson’s disease, a normal soluble protein in the brain called alpha-synuclein can harden into a deposit called a Lewy body.

“Interestingly, lecanemab, the anti-amyloid drug recently reported as beneficial, does something that most other anti-amyloid treatments don’t do in addition to reducing amyloid: it increases the levels of the soluble amyloid-beta,” Espay said

If the root cause is addressed, the levels of the protein wouldn’t need to be boosted because there would be no transformation from soluble, normal proteins to amyloid plaques