Research Overview —
Both apolipoprotein E (apoE) and mitochondrial dysfunction are fundamentally associated with the neurodegenerative processes central to Alzheimer’s disease, yet our understanding of their mutual role in disease pathology remains incomplete. It has previously been reported that neurotoxic fragments of apoE, especially the ε4 variant, can disrupt mitochondrial function and contribute to neuronal metabolic insufficiency and consequent cell death. We have discovered a converse relationship, in which a primary mitochondrial dysfunction profoundly increases apoE expression in a neuronal model, revealing that apoE and mitochondrial biology are more intimately connected than previously thought. The immediate objective of my doctoral research is to characterize the signaling mechanisms that link mitochondrial dysfunction with the profound upregulation of apoE production in these mitochondrial-deficient cells. The ultimate purpose is to use this knowledge to generate pharmaceutical treatments for AD that modulate neurotoxic apoE production and protect mitochondrial function—potentially succeeding where Aβ-targeting therapies have failed.
Gabrielli AP, Weidling I, Ranjan A, Wang X, Novikova L, Chowdhury SR, Menta B, Berkowicz A, Wilkins HM, Peterson KR, Swerdlow RH. Mitochondria Profoundly Influence Apolipoprotein E Biology. J Alzheimers Dis. 2023;92(2):591-604. doi: 10.3233/JAD-221177. PMID: 36776072.
Wang X, Berkowicz A, King K, Menta B, Gabrielli AP, Novikova L, Troutwine B, Pleen J, Wilkins HM, Swerdlow RH. Pharmacologic enrichment of exosome yields and mitochondrial cargo. Mitochondrion. 2022 May; 64:136-144. doi: 10.1016/j.mito.2022.04.001. Epub 2022 Apr 6. PMID: 35398304; PMCID: PMC9035121.
Gabrielli AP, Manzardo AM, Butler MG. GeneAnalytics Pathways and Profiling of Shared Autism and Cancer Genes. Int J Mol Sci. 2019 Mar 7; 20(5):1166. doi: 10.3390/ijms20051166. PMID: 30866437; PMCID: PMC6429377.
Gabrielli A, Poje AB, Manzardo A, Butler MG. STARTLE RESPONSE ANALYSIS OF FOOD-IMAGE PROCESSING IN PRADER-WILLI SYNDROME. J Rare Disord. 2018 Oct; 6(1):18-27. PMID: 30637262; PMCID: PMC6326586.
Gabrielli AP, Manzardo AM, Butler MG. Exploring genetic susceptibility to obesity through genome functional pathway analysis. Obesity (Silver Spring). 2017; 25(6):1136-1143. doi:10.1002/oby.21847
Gabrielli AP. Primary Mitochondrial Dysfunction Promotes Apolipoprotein E Upregulation in a Neuronal Model (An Update). April 11, 2023. Presented at the University of Kansas Medical Center Student Research Forum.
Gabrielli AP. Primary Mitochondrial Dysfunction Promotes Apolipoprotein E Upregulation in a Neuronal Model. April 5, 2022. Presented at the University of Kansas Medical Center Student Research Forum.
Gabrielli AP. Mechanisms of neuronal APOE induction in the setting of primary mitochondrial dysfunction. June 28, 2021. Presented at the KUMC MD-PhD Program Annual Retreat.
Gabrielli AP. Mechanisms of neuronal APOE induction in the setting of primary mitochondrial dysfunction. April 7, 2021. Presented at the University of Kansas Medical Center Student Research Forum.
Gabrielli AP, Demingy Y, Del-Aguila J, Dube U, & Cruchaga C. Assessment of Genetic Burden through Polygenic Risk Scoring for Alzheimer’s and Related Endophenotypes. August 4, 2017. Presented at the Washington University in St. Louis Department of Biology and Biomedical Sciences Research Symposium.
Gabrielli AP, Swerdlow RH. Primary mitochondrial dysfunction promotes APOE upregulation in neuronal models. Society for Neuroscience Annual Meeting, 2023.
Awards and Honors —
- Joan S. Hunt Award (2023)
- Brain Health Training Program Graduate Scholar (2023)
- Biomedical Research Training Program Fellowship (2023)
- Karen B. and Kelly D. Gregg Graduate Student Alzheimer’s Disease Research Award (2022)