posted on 2024-01-18, 14:16authored byMelanie
T. Odenkirk, Xueyun Zheng, Jennifer E. Kyle, Kelly G. Stratton, Carrie D. Nicora, Kent J. Bloodsworth, Catriona A. Mclean, Colin L. Masters, Matthew E. Monroe, James D. Doecke, Richard D. Smith, Kristin E. Burnum-Johnson, Blaine R. Roberts, Erin S. Baker
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)
ε4-allele carriers in AD relative to healthy cohorts. Thus,
the resulting molecular changes in 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 AD and 29 controls (Ctrl) were studied to balance
the number of ε4-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,
ε4 allele carriers (APOE4+ for those carrying 1 or 2 ε4s
and APOE4– for non-ε4 carriers), and differences in ε3ε3
and ε3ε4 Ctrl brains across two brain regions (frontal
cortex (FCX) and cerebellum (CBM)). 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.