Sex-specific Alzheimer's treatment could benefit males over females

December 21, 2020

A University of Ottawa study has found a specific Alzheimer's treatment is effective in male and not female mice, providing a window into the biology of the disease and the effectiveness of targeted treatments.

The paper, 'AB oligomers induce pathophysiological mGluR5 signaling in Alzheimer's disease model mice in a sex-selective manner', published in Science Signaling Magazine highlights the mechanisms underlying Alzheimer's disease are fundamentally different between men and women in regards to one specific treatment.

The study was led by first author Dr. Khaled Abdelrahman alongside senior author Dr. Stephen Ferguson, both of the Faculty of Medicine's Department of Cellular and Molecular Medicine and the Brain and Mind Research Institute.

Dr. Abdelrahman shared some insights into the findings.

What exactly did you set to study?
"The research involved assessing the memory function in female and male Alzheimer's mice after they were treated with a drug that selectively blocks a receptor to regulate memory and learning. We then assessed the recovery of memory deficits after treatment and how it is different between sexes. We also examined whether the binding of a toxic Ab; peptide to this receptor is different between male and female mouse and human brain." (Note: An AB peptide is found in the brain of an Alzheimer's patient and is a hallmark of the disease.)

What did you find?
"We showed at least one promising Alzheimer's disease treatment was effective in reversing the disease in male mice but that it was unable to do so in female mice. This will have important implications for future drug discovery and clinical trials design for Alzheimer's disease."

How do these findings translate to humans?
"We utilized post-mortem brain tissue from male and female human donors to corroborate our findings. The benefit to humans is that these selective differences may be applicable to many drugs in the market or in clinical trial phases."

What kind of impact can this discovery have?
"We have to be careful when designing clinical trials in the future since many drug candidates have the opposite or different outcomes for both sexes; not all drugs that work for men will work with women, and vice-versa. It also changes how clinical trial data should be evaluated and segregated by sex. Importantly, it defines a previously unknown differences in the biophysical properties of an important receptor in the brain that regulates memory and learning."

What was your reaction to these findings?
"As a pharmacist, I have witnessed many patients in practice who struggle with Alzheimer's disease and ineffective treatments. This motivated me to make effort in understanding the mechanisms that lead to the disease for better therapeutic approaches to be undertaken."
-end-


University of Ottawa

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.