Authors:

Ann Titus

Date Created:

Not specified

Course Title:

Professor:

Not specified

About Paper:

Alzheimer's disease (AD), characterized by the accumulation of beta-amyloid plaques and neurofibrillary tau tangles, is anticipated to impact 13 million Americans by 2050. While research has primarily focused on disease progression and treatments, recent studies highlight the undeniable involvement of the immune system in AD development. Microglia, the frontline defenders in the central immune system, exhibit dual effects based on genetic variants. The P522R variant in the phospholipase C gamma 2 (PLCG2) enzyme gene has emerged as protective in AD, enhancing microglial phagocytosis and inflammation. This peculiar variant's ability to be both inflammatory and protective is crucial given inflammation's connection to AD-associated cognitive decline. The protective role of P522R suggests its impact before cognitive decline onset, indicating potential differences in the inflammation pathway. To probe the preclinical function of this variant, 10 female mice brains, both with and without the variant, were dissected at 5 months. Brain regions (cortex, hippocampus, and striatum) were isolated, and gene expression was analyzed using qPCR. Various genes associated with inflammation and activated/homeostatic microglia were examined to understand regional immune cell function differences. In exploring major inflammatory pathways (IL- 10, IL-6, and TNF expression), IL-10 levels were too low to quantify. Notably, no significant differences were observed between variant and nonvariant mice in IL-6 and TNF expression, indicating consistent regional gene expression compared to wild-type mice. Future experiments will involve inflammatory stimulants like lipopolysaccharide, enabling assessment of inflammatory gene expression in these brain regions under immune-activated conditions, providing valuable insights into the complex interplay between genetics, immune response, and AD progression. Medicine 140

Source:

University of Florida / Ann Titus, Hannah Staley, Malú Tansey / 2023

Topics:

No topics listed

Co-authors:

Ann Titus