The study published in the American Journal of Human Genetics reveals a groundbreaking approach to understanding Alzheimer’s disease. By integrating computational and functional methods, researchers at Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute (Duncan NRI) have identified potential risk factors and targets for therapeutic intervention. The breakthrough findings shed light on the complex causes of Alzheimer’s disease, which affects over 50 million people worldwide.

The study’s lead author, Dr. Juan Botas, emphasized that despite extensive genome-wide studies, the roles of many genes in Alzheimer’s disease were still unclear. “We addressed this issue by integrating published genome-wide association data with multiple computational approaches to identify genes likely involved in AD,” said Dr. Botas. This innovative approach enabled the researchers to pinpoint not only specific genes associated with increased risk but also those that could potentially modulate neuronal dysfunction.

The team systematically assessed 123 candidate genes for their potential impact on Alzheimer’s disease and found that reversing the alterations in 11 of these genes protected fruit flies from damage to their nervous system. Notably, one gene, MTCH2, emerged as a top contender for therapeutic purposes. The researchers discovered that reducing MTCH2 expression in fruit flies aggravated motor dysfunction, while restoring its expression reversed motor impairment and reduced tau accumulation.

“This finding supports further exploration of MTCH2 for therapeutic purposes and highlights the value of a combined computational and experimental approach to uncover main genetic players in Alzheimer’s disease,” said Dr. Botas.

The study’s authors note that this work was supported by NIH grants, underscoring the importance of continued research in this area. As scientists continue to unravel the complexities of Alzheimer’s disease, their findings hold promise for future therapeutic interventions and improved patient outcomes.

The article “Early Menopause Linked to Cognitive Decline: A Study on Women’s Risk Factors” reveals a significant link between early menopause and cognitive decline in women. Researchers from Tohoku University Graduate School of Medicine and Tokyo Metropolitan Institute of Medical Science conducted a study that analyzed the English Longitudinal Study of Ageing, which included 4,726 women and 4,286 men. The team found that women who entered menopause before the age of 40 had worse cognitive outcomes compared to those who entered menopause after the age of 50.

The researchers were motivated by the disproportionate impact of dementia on women worldwide, as well as the association between early menopause and higher risk of depression in later life. The team controlled for modifiable risk factors for dementia and found that menopause at <40 years was significantly associated with worse cognitive function over a two-year follow-up period. Interestingly, the study also showed that hormone replacement therapy (HRT) did not have an association with cognitive function. This suggests that early menopause may be a direct risk factor for cognitive decline in women. The researchers concluded that understanding this relationship could potentially help design treatments to delay the onset of dementia in at-risk patients. The implications of this study are significant, as it highlights the importance of considering sex-specific factors when assessing the risk of developing dementia. Further research is warranted to elucidate the underlying mechanisms of the relationship between levels of female hormones and cognitive function.

In a groundbreaking study published in Neurology®, researchers have shed light on how age, sex, hormonal changes, and genetics influence certain biomarkers for dementia in the blood. The study, led by Hannah Stocker, PhD, MPH, of Heidelberg University in Germany, provides valuable insights into the roles these factors play in shaping an individual’s risk of developing dementia.

The researchers analyzed data from a larger 17-year study involving 513 people who developed dementia and 513 who remained free of the condition. The participants had an average age of 64 at the start of the study. By taking blood samples three times during the study, the researchers measured levels of three biomarkers: neurofilament light chain proteins, glial acidic proteins, and phosphorylated tau 181.

The findings revealed that older age was associated with higher levels of all three markers. For example, people aged 75 had an average of 25 picograms per milliliter (pg/ml) for neurofilament light chain proteins compared to those aged 50 who averaged 10 pg/ml. Similarly, glial acidic proteins were found at higher levels in older participants, with a significant difference between those aged 75 and those aged 50.

The study also showed that female participants had higher levels of glial acidic proteins, while male participants had higher levels of neurofilament light chain proteins. Furthermore, the researchers discovered that people who carried the APOEe4 gene had higher levels of tau and glial acidic proteins.

Notably, the study found that female participants who had not yet gone through menopause had higher levels of glial acidic proteins. This may be attributed to having higher levels of sex hormones, which have been linked to neuroinflammation in previous studies.

The findings of this study highlight the importance of further exploring these biomarkers, including during menopause, in the development of dementia. By gaining a better understanding of how age, sex, hormonal changes, and genetics interact with biomarker levels, researchers can improve their ability to test for dementia using simple blood tests.