Mitochondrial Dysfunction Greater in Brain Proteins of Women with Dementia Than Men, Study Finds

Researchers have, for the first time, detected differences in proteins in the brains of men and women with dementia. The findings advance understanding of the molecular differences underlying an increased dementia risk in women, and might pave the way for better interventions for men and women alike. They also re-enforce the idea that mitochondrial dysfunction is linked to dementia.

“The number of dementia patients is projected to triple by 2050 and there is an urgent need to identify key mechanisms of how dementia develops. Our findings and further study could have direct implications for our knowledge about the progression of dementia that could lead to the development of drugs for treatment of dementia,” Sze Siu Kwan, an associate professor in the School of Biological Sciences at Nanyang Technological University, Singapore, and the study’s senior author, said in a press release.

Researchers explored potential disease-associated changes in post-mortem brains from five men and five women who had dementia, and in 10 control individuals. The team used a proteomics approach — studying a large set of proteins without predefined notions that any particular protein might be linked to disease.

Particularly, the scientists were searching for changes in the proteins’ structure and function in the white matter and mitochondria, focusing on the temporal lobe. This brain region is crucial for visual memory processing and the understanding of language, two processes that are impaired in patients with dementia.

The study, “Gender differences in white matter pathology and mitochondrial dysfunction in Alzheimer’s disease with cerebrovascular disease,” found that a protein involved in the production of myelin — which forms a layer of insulation on nerve cell axons — was among the proteins most affected by the so-called degenerative protein modifications.

Axons are the long nerve cell processes that send signals from one neuron to another, and the insulation is needed to speed up the process. This myelin basic protein (MBP) was significantly altered in a way that made the protein lose its function, contributing to a loss of myelin and disrupted communication between nerve cells. Intriguingly, the team found the modifications to the MBP were more pronounced in women.

“The findings of this study indicate that proteomics can detect differences between male and female dementia patients on a molecular level which cannot be detected by standard approaches,” Xavier Gallart-Palau, the study’s first author, said in the release.

“As degenerative protein modifications are likely to critically influence protein function and activity in the central nervous system, they can be novel drug targets for treatment of dementia,” added Dr. Kwan.

In the study, published in the journal Molecular Brain, the team also noted that dementia patients had very low levels of certain proteins in the mitochondria, indicating that these cellular powerhouses are dysfunctional. Again, the changes in the mitochondrial proteins were more severe in women. These results add evidence to the notion that dementia might, at least in part, be caused by mitochondrial dysfunction.