Therapeutics to protect brain function and mitigate risk for Alzheimer’s disease

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Did you know that the development of Alzheimer’s disease actually starts in the brain 20 to 30 years before any dementia symptoms appear? This is particularly true for people who carry the Apolipoprotein e4 (APOE4) gene, which is the most significant genetic risk factor for Alzheimer’s. Individuals with one or two copies of the APOE4 gene have a 4- to 8-fold higher risk of developing the disease and may experience symptoms 7 to 15 years earlier than those without the gene. Interestingly, even in their 20s and 30s, young individuals who are cognitively normal but carry the APOE4 gene have shown reduced brain blood flow and metabolism, even before the accumulation of amyloid beta plaques or tau tangles.

Finding interventions that can restore the brain’s vascular and metabolic functions before Alzheimer’s symptoms appear is crucial in reducing the risk of developing the disease.

One potential intervention that has been studied is a drug called Rapamycin, which is already approved by the FDA for other purposes. In a recent study, we performed experiments with mice carrying the human APOE4 gene and studied effects of Rapamycin to mitigate risk for Alzheimer’s disease. The findings revealed that after 4 months of Rapamycin treatment, APOE4 mice had improved cerebral blood flow, enhanced brain metabolism, and better recognition memory compared to mice on a control diet. Rapamycin also significantly reduced the accumulation of amyloid plaques and protected the integrity of the blood-brain barrier in the mice. These results demonstrate the effectiveness of Rapamycin in restoring brain function and lowering the risk of Alzheimer’s in asymptomatic mice carrying the APOE4 gene.

Our findings also shows that it is crucial to preserve brain vascular and metabolic functions to protect against cognitive impairment. Since Rapamycin is already FDA-approved and neuroimaging techniques are available for humans, clinical trials are currently being conducted in our laboratory to further explore the potential benefits of Rapamycin for individuals with the APOE4 gene. The goal is to identify effective interventions that can reduce the risk of Alzheimer’s disease in those who are genetically predisposed.

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