How does Alzheimer’s disease kill brain cells? Scientists discover the answer

CHICAGO — A new study is finally revealing the process by which Alzheimer’s disease devastates brain cells. Alzheimer’s disease affects approximately 55 million people globally and leads to a significant loss of neurons (brain cells). For a long time, scientists have struggled to identify the causes of this neuron loss. However, recent research conducted by researchers at Northwestern Medicine suggests that RNA interference might play a crucial role.

Ribonucleic acids (RNAs) are vital for most biological functions. Yet, as individuals age, RNAs can transition from being protective to becoming toxic. The study discovered that short strands of these toxic RNAs, known as sRNAs, contribute to the death of brain cells and DNA damage. This finding highlights a critical factor in the development of Alzheimer’s disease.

“Nobody has ever before connected the activities of sRNAs to Alzheimer’s. But we have found that, in ageing brain cells, the balance between toxic and protective sRNAs shifts toward toxic ones,” says corresponding study author Dr. Marcus Peter from Northwestern University, according to a statement from SWNS.

The study’s findings have identified potential new approaches to treating Alzheimer’s disease.

Since Alzheimer’s is a progressive development of amyloid-beta plaques, tau neurofibrillary tangles, and ultimately, brain cell death, most research efforts have concentrated on these aspects in the search for a cure.

“The overwhelming investment in Alzheimer’s drug discovery has been focused on two mechanisms: reducing amyloid plaque load in the brain – which is the hallmark of Alzheimer’s diagnosis and 70 to 80 percent of the effort – and preventing tau phosphorylation or tangles,” Dr. Peter explains.

However, these treatments have so far proved unsuccessful, meaning a different approach – like looking at sRNAs – may be the answer people have been looking for.

“Treatments aimed at reducing amyloid plaques have not yet resulted in an effective treatment that is well tolerated,” Dr. Peter says, according to SWNS. “Our data supports the idea that stabilizing or increasing the amount of protective short RNAs in the brain could be an entirely new approach to halt or delay Alzheimer’s.”

The study authors add that the research can also help with the treatment of other neurogenerative diseases, meaning the implications of the study are even wider.

“We have a new explanation for why, in almost all neurodegenerative diseases, affected individuals have decades of symptom free life and then the disease starts to set in gradually as cells lose their protection with age,” Dr. Peter notes.

The study, published in Nature Communications, examined the brains of Alzheimer’s disease mouse models, as well as the brains of both young and old mice. It also included neurons from individuals with and without Alzheimer’s, and a group of elderly individuals over 80 who had memory capabilities comparable to those between 50 and 60 years-old.

The findings revealed that older patients, and those with Alzheimer’s, possessed higher levels of toxic short strands of RNAs (sRNAs). In contrast, younger individuals and those over 80 with better memory capacity exhibited higher levels of protective sRNAs.

Normally, RNAs are instrumental in protein production. However, the research team from Northwestern Medicine discovered that toxic RNAs can lead to cell death by hindering the production of essential proteins necessary for cell survival.

“Our data suggests that these toxic sRNAs are involved in the death of neurons which contributes to the development of Alzheimer’s disease,” Dr. Peter explains. “The toxic sRNAs are normally inhibited by protective sRNAs. But their numbers decrease with ageing, thus allowing the toxic sRNAs to damage the cells.”

Dr. Peter’s next phase of research will focus on determining the precise role of toxic short strands of RNAs (sRNAs) in causing cell death in Alzheimer’s disease. This investigation will be conducted across various animal and cellular models, as well as in the brains of Alzheimer’s patients.

Subsequently, he aims to identify compounds that could either elevate the levels of protective sRNAs or inhibit the action of the toxic ones.

South West News Service writer Imogen Howse contributed to this report.