How does the brain respond to Alzheimer’s? Research suggests it may try to protect certain areas

A recent study by researchers from the U.K. and New Zealand produced the largest dataset of region-specific protein expression in six functionally distinct regions of a human Alzheimer’s brain, namely the hippocampus, cingulate gyrus, entorhinal cortex, sensory cortex, motor cortex, and cerebellum. The study was published in the journal Communication Biology and is available online for anyone to access.

In a statement, lead researcher Richard Unwin from The University of Manchester said that the database gives many researchers around the world the opportunity to develop their own treatments, as well as progress and follow-up new areas of biology. They could also use the database to validate observations previously seen in animal or cell disease models.

“It’s very exciting to be able to make these data public so scientists can access and use this vital information,” he added.

Alzheimer’s disease harms certain regions of the brain more than others

Unwin and his team analyzed the expression data of over 5,500 proteins in the post-mortem tissues of nine healthy and nine Alzheimer’s patients. This allowed the team to identify changes related to Alzheimer’s disease across different brain regions, revealing dozens of proteins that have not been associated with the disease and areas of the brain that are more affected than others.

In particular, Alzheimer’s disease heavily affects the hippocampus, the entorhinal cortex, and the cingulate gyrus. The cerebellum, previously thought to be less damaged by the disease, revealed significant changes in protein expression.

“The cerebellum, previously thought to be unaffected [by Alzheimer’s], displays a significant response at the molecular level,” Unwin explained. “Many of the changes here are not seen in other regions and this could imply that [the human cerebellum] actively protects itself from Alzheimer’s disease.”

According to first author Jingshu Xu, this so-called neuroprotective ability of the cerebellum could be caused by two things: a distinct protein expression profile and an up-regulated neuronal survival pathway. A deep dive into the matter revealed that the cerebellum has lower levels of a protein called electron transport chain (ETC) complex 1 compared to other areas. The area also has elevated levels of antioxidant proteins that are involved in glutathione redox reactions and ascorbate recycling.

These phenomena, the researchers proffered, suggest that the cerebellum has a protective mechanism that reduces the production of harmful reactive oxygen species (ROS) by the ETC, while simultaneously boosting its defenses against it.

The findings of the study were in the same vein. The lack of neurodegeneration in the area wasn’t because of the lack of tau tangles responsible for signaling cell death; instead, the researchers found that this was because of the up-regulation of neuronal survival pathways, which protected the cerebellum from oxidative and inflammatory damage.

This created “a protective mechanism of gene/protein expression, which limits disease-related degeneration in this region,” they wrote.

A leading cause of death that has no known cure

In the U.S., over five million adults are currently suffering from Alzheimer’s disease. The progressive disease, which is seen mainly in older adults over age 60, can start with mild memory loss. Over time, it can lead to loss of the ability to carry a conversation and even respond to the patient’s environment.

While the etiology of Alzheimer’s disease is still unclear, experts identify age to be the best-known risk factor for the disease. Recent studies, however, found that risk factors for chronic diseases like hypertension, heart disease, and stroke can similarly increase the risk of developing Alzheimer’s disease. (Related: Antiepileptic drugs have NO place in Alzheimer’s treatments: Study reveals they cause longer hospital stays in patients.)

Currently, there is no known cure for Alzheimer’s disease.

Sources include:

Newswise.com

The-Scientist.com

PsychologyToday.com

CDC.gov