A recent study could shed light on the greater susceptibility of women to Alzheimer’s disease, offering potential breakthroughs for pharmaceutical development aimed at protecting individuals, particularly women.
Case Western Reserve University researchers have identified a specific enzyme, ubiquitin-specific peptidase 11 (USP11), expressed at higher levels in female brains. USP11 plays a role in removing ubiquitin, a small protein tag, from various proteins, including tau protein.
Normally, ubiquitin marks proteins for degradation. However, when ubiquitin is removed, proteins can accumulate. In the case of women with elevated USP11 expression, this leads to increased accumulations of tau protein, a key contributor to the toxic buildup of protein clumps characteristic of Alzheimer’s disease.
While it has been established for some time that women are diagnosed with Alzheimer’s more frequently than men, the prevailing belief attributed this to women’s longer life expectancy. Nevertheless, the new research opens the door to exploring other contributing factors.
Nikhil Palekar, MD, Director of the Stony Brook Center of Excellence for Alzheimer’s Disease, suggests that this groundbreaking finding may answer the questions scientists have pondered for years.
Shae Datta, MD, Co-Director of NYU Langone’s Concussion Center, also acknowledges the significance of this research. It reveals a 1.7 times higher likelihood of women having an increased burden and a higher incidence of Alzheimer’s.
However, these findings may raise concerns and questions among the general public. Experts have provided insights into the study’s implications, what it clarifies, what remains unknown, and how individuals can reduce their risk of Alzheimer’s.
Key Findings of the Study
According to David Kang, PhD, the Howard T. Karsner Professor in Pathology at the Case Western Reserve School of Medicine and co-senior author of the study, the research initially aimed to identify enzymes responsible for removing ubiquitin from the tau protein. This objective stemmed from the intricate balance of enzymes that regulate the presence of ubiquitin on tau. Any malfunction in this process can result in the abnormal accumulation of tau, a hallmark of Alzheimer’s.
Unexpectedly, the study revealed that USP11 was present on X chromosomes, even in women without dementia. Typically, one of the X chromosomes is mostly inactive in women, but certain genes on the X chromosome can escape this inactivation, including USP11.
In an animal model where USP11 was genetically removed, the results indicated potential protection against tau accumulation and cognitive decline in females.
In simpler terms, having two X chromosomes elevates the levels of an enzyme linked to brain protein aggregation, a contributing factor to Alzheimer’s disease. Inhibiting USP11 may offer a way to mitigate the increased Alzheimer’s risk in women.
David Kang views this study as a reason for hope, as it pinpoints a potential cause of Alzheimer’s in women, providing an opportunity for intervention.
The applicability of the findings from the animal model to humans may require further investigation.
Furthermore, the treatments developed based on these findings could benefit individuals with other conditions associated with tau accumulation, such as multiple system atrophy (MSA), corticobasal degeneration, frontotemporal dementia, and chronic traumatic encephalopathy (CTE).
Other Factors Influencing Alzheimer’s Risk
Nikhil Palekar underscores that while women are more susceptible to Alzheimer’s, their biological sex is not the sole contributing factor. Other elements include:
- Brain Inflammation
- Age
- Genetics
- Hypertension (High Blood Pressure)
- High Cholesterol
- Diabetes
Alzheimer’s can run in families somewhat, although it is not certain. While researchers haven’t identified a specific gene directly responsible for late-onset Alzheimer’s, the National Institutes of Health (NIH) and Palekar mention that individuals with a genetic variant of apolipoprotein E (APOE) on the 19th chromosome have an elevated Alzheimer’s risk. This gene plays a role in producing a protein that transports fats in the bloodstream.
Moreover, conditions like diabetes and high blood pressure can affect the brain by reducing blood flow by narrowing blood vessels, potentially increasing Alzheimer’s risk. Hence, focusing solely on tau protein isn’t the solution.
Alzheimer’s Prevention
It’s important to acknowledge that not all aspects of Alzheimer’s risk can be controlled, such as biological sex and genetics. According to Laurence Miller, Ph.D., a clinical and forensic psychologist and adjunct professor at Florida Atlantic University, there’s no magic solution for preventing Alzheimer’s. Instead, maintaining positive health practices benefits both the brain and the body.
Palekar emphasizes that, even with inherent risk factors like biological sex or family history, individuals can take steps to reduce their Alzheimer’s risk. These measures include:
- Regular Exercise
- Managing Conditions like Diabetes and Cardiovascular Disease through Medication and Treatment
- Healthy Diet
- Social Interaction
- Mental Stimulation through Work, Games, and Puzzles
Research increasingly suggests that physical activity may lower the risk of developing Alzheimer’s, as indicated in a 2020 literature review. Palekar recommends aiming for 150 minutes of moderate-intensity exercise weekly, equivalent to 30 minutes of activity on five days per week.
This aligns with the Physical Activity Guidelines for Americans, as established by the U.S. Department of Health and Human Services.
A study from 2015 involving over 900 participants aged 58 to 98 demonstrated that adhering to the MIND diet, a blend of Mediterranean and DASH diets potentially mitigates cognitive decline.
These dietary plans emphasize lean proteins, fruits, vegetables, and healthy fats like olive oil while discouraging the consumption of ultra-processed foods, sugars, and excessive salt.
Furthermore, a literature review in 2018 suggests a growing body of evidence linking feelings of isolation to an increased risk of Alzheimer’s.
In 2018, a small-scale study involving 100 cognitively healthy adults over 50 indicated that engaging in activities like jigsaw puzzles might help preserve cognitive abilities over the long term.