PRIYA PRAKASH - Amyloid-β induces lipid droplet-mediated microglial

Journal article

Priya Prakash*, Palak Manchanda*, Evi Paouri, Kanchan Bisht, Kaushik Sharma, Jitika Rajpoot, Victoria Wendt, Ahad Hossain, Prageeth R Wijewardhane, Caitlin E Randolph, Yihao Chen, Sarah Stanko, Nadia Gasmi, Anxhela Gjojdeshi, Sophie Card, Jonathan Fine, Krupal P Jethava, Matthew G Clark, Bin Dong, Seohee Ma, Alexis Crockett, Elizabeth A Thayer, Marlo Nicolas, Ryann Davis, Dhruv Hardikar, Daniela Allende, Richard A Prayson, Chi Zhang, Dimitrios Davalos, Gaurav Chopra
Immunity, 2025

DOI: 10.1016/j.immuni.2025.04.029

Semantic Scholar DOI PubMed

Cite

APA Click to copy
Prakash*, P., Manchanda*, P., Paouri, E., Bisht, K., Sharma, K., Rajpoot, J., … Chopra, G. (2025). Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer's disease. Immunity. https://doi.org/10.1016/j.immuni.2025.04.029

Chicago/Turabian Click to copy
Prakash*, Priya, Palak Manchanda*, Evi Paouri, Kanchan Bisht, Kaushik Sharma, Jitika Rajpoot, Victoria Wendt, et al. “Amyloid-β Induces Lipid Droplet-Mediated Microglial Dysfunction via the Enzyme DGAT2 in Alzheimer's Disease.” Immunity (2025).

MLA Click to copy
Prakash*, Priya, et al. “Amyloid-β Induces Lipid Droplet-Mediated Microglial Dysfunction via the Enzyme DGAT2 in Alzheimer's Disease.” Immunity, 2025, doi:10.1016/j.immuni.2025.04.029.

BibTeX Click to copy

@article{priya2025a,
  title = {Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer's disease},
  year = {2025},
  journal = {Immunity},
  doi = {10.1016/j.immuni.2025.04.029},
  author = {Prakash*, Priya and Manchanda*, Palak and Paouri, Evi and Bisht, Kanchan and Sharma, Kaushik and Rajpoot, Jitika and Wendt, Victoria and Hossain, Ahad and Wijewardhane, Prageeth R and Randolph, Caitlin E and Chen, Yihao and Stanko, Sarah and Gasmi, Nadia and Gjojdeshi, Anxhela and Card, Sophie and Fine, Jonathan and Jethava, Krupal P and Clark, Matthew G and Dong, Bin and Ma, Seohee and Crockett, Alexis and Thayer, Elizabeth A and Nicolas, Marlo and Davis, Ryann and Hardikar, Dhruv and Allende, Daniela and Prayson, Richard A and Zhang, Chi and Davalos, Dimitrios and Chopra, Gaurav}
}

Abstract

Microglial phagocytosis genes have been linked to increased risk for Alzheimer’s disease (AD), but the mechanisms translating genetic association to cellular dysfunction remain unknown. Here, we showed that microglia formed lipid droplets (LDs) upon amyloid-β (Aβ) exposure and that LD loads increased with proximity to amyloid plaques in brains from individuals with AD and the 5xFAD mouse model. LD-laden microglia exhibited defects in Aβ phagocytosis, and unbiased lipidomic analyses identified a parallel decrease in free fatty acids (FFAs) and increase in triacylglycerols (TGs) as the key metabolic transition underlying LD formation. Diacylglycerol O-acyltransferase 2 (DGAT2)—a key enzyme that converts FFAs to TGs—promoted microglial LD formation and was increased in mouse 5xFAD and human AD brains. Pharmacologically targeting DGAT2 improved microglial uptake of Aβ and reduced plaque load and neuronal damage in 5xFAD mice. These findings identify a lipid-mediated mechanism underlying microglial dysfunction that could become a therapeutic target for AD.