Molecular Differences in Alzheimer’s Disease Between Male and Female Patients

By Nicole Zhao ‘20 

Alzheimer'sBrainComparison
Figure 1. Although there has been extensive research on the physical and biological differences in Alzheimer’s patients, the impact of sex differences on the disease has yet to be explored. 

Alzheimer’s disease is a neurodegenerative disorder that causes memory, cognitive  and behavioral problems (1). In the United States, approximately 5.5 million people live with Alzheimer’s with two-thirds being women (2). Although  Alzheimer’s treatments are heavily researched, the impact of sex on the molecular level of the disease has not been explored. In this article, sex refers to the physiological and biological differences between men and women (2). In a new study conducted by researchers at The First Affiliated Hospital of Harbin Medical University in Harbin, China, a global gene expression analysis was conducted between normal subjects and patients diagnosed with Alzheimer’s disease. 

It was found that no genes were expressed differently between normal subjects and male and female Alzheimer’s patients (3). However, a region-specific analysis showed that the number of differentially expressed genes varied greatly (7-46 genes) across 17 regions of the brain in 125 individuals with Alzheimer’s disease (3). This means that although the total expressed genes did not differ between normal subjects and patients with Alzheimer’s, the genes expressed in different areas of the brain varied. The ESRRB gene that encodes the oestrogenrelated receptor beta was one gene that was only shared in 4 out of the 17 studied regions of the brain (3). The ligand to the receptor, oestrogen, has previously been found to be involved in cognition and memory (3). Previous research has also found that oestrogen levels decline in the brain post-menopause in females (4). This decline may make neurons more susceptible to neurodegeneration processes due to aging. Thus, this gene may contribute to sex-related differences in Alzheimer’s patients. 

The ESRRB gene that was found in only four regions of the brain may be a potential therapeutic target for Alzheimer’s since oestrogen levels are different in females and males in the later years of life. This study emphasizes a greater need in understanding how sex differences impact this Alzheimer’s disease on a molecular impact. If we can accomplish this, physicians may be able to develop new drugs to target the causes or symptoms of Alzheimer’s in a more individual basis.

References:

  1. What is Alzheimer’s? Alzheimer’s Association
  2. C. Toro, et al., Sex differences in Alzheimer’s disease: understanding the molecular impact. Brain Research 1719, 194-207 (2019). doi: 10.1016/j.brainres.2019.05.031. 
  3. S. Lin-Lin, et al., Molecular differences in Alzheimer’s disease between male and female patients determined by integrative network analysis. Journal of Cellular and Molecular Medicine 23, 47-58 (2019). doi: 10.1111/jcmm.13852. 
  4. C. Coffey, et al., Sex differences in brain aging: a quantitative magnetic resonance imaging study. Archives of Neurology 55, 169-79 (1998). doi: 10.1001/archneur.55.2.169
  5. Image retrieved from: https://commons.wikimedia.org/wiki/
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