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2021 Alzheimer's Association Research Grant (AARG)

AD Pathological Features Driven by Blood-Borne Factors

Can proteins in aged blood impact brain changes associated with Alzheimer’s?

Joseph Castellano, Ph.D.
Icahn School of Medicine at Mount Sinai
New York, NY - United States


Aging is the biggest risk factor for Alzheimer’s. Studies indicate that there may be proteins in the blood that can drive aging. Researchers have shown that proteins that accumulate with age in the blood may impact the onset and progression of Alzheimer’s.

In preliminary studies, Dr. Joseph Castellano and colleagues found that a protein called MMP2, which is found in the blood and is associated with young age, may be able to rejuvenate the hippocampus- a brain region important for learning and memory and impacted early in Alzheimer’s - when given to aged mice. They have also found that giving blood from aged mice to young genetically engineered Alzheimer’s-like mice could accelerate the development of brain changes observed in Alzheimer’s in these mice. Additionally, the researchers found that giving blood from aged mice to young genetically engineered Alzheimer’s-like mice could also impact changes in microglia; microglia are the primary immune cells of the brain and help maintain healthy nerve cells in the brain. Individuals with Alzheimer’s typically experience brain inflammation caused by dysregulation of the immune system, including increased activity of microglia, which can damage the nearby nerve cells.

Research Plan

Dr. Castellano’s team will leverage their preliminary findings to further study proteins in the blood associated with aging and their potential impact on the development of Alzheimer’s. They will use young genetically engineered Alzheimer’s-like mice and administer blood from aged cognitively unimpaired mice.  Dr. Castellano’s team will then study whether the exposure to aged blood impacts the levels of beta-amyloid plaques in the Alzheimer’s-like mice; the beta-amyloid protein accumulates to form plaques, one of the hallmark brain changes observed in Alzheimer’s. 

Further, the researchers will perform additional experiments to study the impact of aged blood exposure to the Alzheimer’s-like mice. Dr. Castellano’s team will compare genes in the DNA (genetic material) that may be activated in the microglia with or without exposure to aged blood. Finally, Dr. Castellano’s team will also compare changes in the specialized nerve cell structures through which nerve cells communicate with each other (called synapses), as well as changes in the behavior of Alzheimer’s-like mice with and without exposure to aged blood.


The study results may help in understanding how proteins found in aged blood may impact brain changes observed in Alzheimer’s. If successful, the results may eventually help in developing potential blood-based diagnostics and therapies for Alzheimer’s.

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