Alzheimer’s disease (AD) is a neurodegenerative disease with a complex etiology influenced by confounding factors such as genetic polymorphisms, age, sex, and race. Traditionally, AD research has not prioritized these influences, resulting in dramatically skewed cohorts such as three times the number of Apolipoprotein E (APOE) e4-allele carriers in AD relative to healthy cohorts. Thus, the resulting molecular changes of AD have previously been complicated by the influence of apolipoprotein E disparities. To explore how apolipoprotein E polymorphism influences AD progression, 62 post-mortem patients consisting of 33 Alzheimer’s disease (AD) and 29 controls (Ctrl) were studied to balance the number of e4-allele carriers and facilitate a molecular comparison of the apolipoprotein E genotype. Lipid and protein perturbations were assessed across AD diagnosed brains compared to Ctrl brains, e4 allele carriers (APOE4+ for those carrying 1 or 2 e4s and APOE4- for non-e4 carriers), and differences in e3e3 and e3e4 Ctrl brains across two brain regions (frontal cortex (FCX) and cerebellum (CBM)). In conclusion, the region-specific influences of apolipoprotein E on AD mechanisms showcased mitochondrial dysfunction and cell proteostasis at the core of AD pathophysiology in the post-mortem brains, indicating these two processes may be influenced by genotypic differences and brain morphology.
Odenkirk, Melanie T., Zheng, Xueyun, Kyle, Jennifer E., Stratton, Kelly G., Nicora, Carrie D., Bloodsworth, Kent J., Mclean, Catriona A., Masters, Colin L., Monroe, Matthew E., Doecke, James D., Smith, Richard D., Burnum-Johnson, Kristin E., Roberts, Blaine R., & Baker, Erin S. (2024). Deciphering ApoE Genotype-Driven Proteomic and Lipidomic Alterations in Alzheimer’s Disease Across Distinct Brain Regions. Journal of Proteome Research, 23(8). https://doi.org/10.1021/acs.jproteome.3c00604
Odenkirk, Melanie T., Zheng, Xueyun, Kyle, Jennifer E., et al., "Deciphering ApoE Genotype-Driven Proteomic and Lipidomic Alterations in Alzheimer’s Disease Across Distinct Brain Regions," Journal of Proteome Research 23, no. 8 (2024), https://doi.org/10.1021/acs.jproteome.3c00604
@article{osti_3008511,
author = {Odenkirk, Melanie T. and Zheng, Xueyun and Kyle, Jennifer E. and Stratton, Kelly G. and Nicora, Carrie D. and Bloodsworth, Kent J. and Mclean, Catriona A. and Masters, Colin L. and Monroe, Matthew E. and Doecke, James D. and others},
title = {Deciphering ApoE Genotype-Driven Proteomic and Lipidomic Alterations in Alzheimer’s Disease Across Distinct Brain Regions},
annote = {Alzheimer’s disease (AD) is a neurodegenerative disease with a complex etiology influenced by confounding factors such as genetic polymorphisms, age, sex, and race. Traditionally, AD research has not prioritized these influences, resulting in dramatically skewed cohorts such as three times the number of Apolipoprotein E (APOE) e4-allele carriers in AD relative to healthy cohorts. Thus, the resulting molecular changes of AD have previously been complicated by the influence of apolipoprotein E disparities. To explore how apolipoprotein E polymorphism influences AD progression, 62 post-mortem patients consisting of 33 Alzheimer’s disease (AD) and 29 controls (Ctrl) were studied to balance the number of e4-allele carriers and facilitate a molecular comparison of the apolipoprotein E genotype. Lipid and protein perturbations were assessed across AD diagnosed brains compared to Ctrl brains, e4 allele carriers (APOE4+ for those carrying 1 or 2 e4s and APOE4- for non-e4 carriers), and differences in e3e3 and e3e4 Ctrl brains across two brain regions (frontal cortex (FCX) and cerebellum (CBM)). In conclusion, the region-specific influences of apolipoprotein E on AD mechanisms showcased mitochondrial dysfunction and cell proteostasis at the core of AD pathophysiology in the post-mortem brains, indicating these two processes may be influenced by genotypic differences and brain morphology.},
doi = {10.1021/acs.jproteome.3c00604},
url = {https://www.osti.gov/biblio/3008511},
journal = {Journal of Proteome Research},
issn = {ISSN 1535-3893},
number = {8},
volume = {23},
place = {United States},
publisher = {American Chemical Society (ACS)},
year = {2024},
month = {01}}