Jessie Blumenfeld

UC San Francisco

“Identifying Disease-promoting and Disease-protecting Factors in the Interstitial Fluids of APOE Mouse Models of Alzheimer’s Disease”

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by a severe decline in memory. Though this disease has been studied for over a century, the biology driving AD remains unclear. Interestingly however, the Apolipoprotein E (APOE) gene has been found to play a critical role in determining AD risk. Of the three major APOE alleles, one – known as APOE4 – increases AD risk by about 12-fold and is considered the greatest genetic risk factor for the disease, while another – APOE2 – actually reduces the likelihood of getting Alzheimer’s by half. Despite the clear role APOE has in determining AD fate, the mechanisms behind how this protein regulates downstream pathologies are not entirely understood. Leveraging interstitial brain fluids collected from disease-destined and disease-resilient APOE models, we aim to characterize the factors downstream of APOE that are AD pathology-inducing or protecting. We aim to uncover key molecular and cellular pathways that are important for triggering the cascade of AD-related pathologies, as well as identify any factors that may provide a useful therapeutic target.


Broadly, I examine the apolipoprotein 4 (APOE4) allele, which is the single greatest genetic risk factor for late-onset Alzheimer’s disease. In particular, I examine the downstream factors and pathways upregulated by APOE4 expression, including various immune factors that seem to trigger classic Alzheimer’s pathologies, such as aggregation of hyperphosphorylated tau, neuron death, and neuroinflammation. Through my research, I hope to identify important targets for halting or slowing the progression of Alzheimer’s pathologies.

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