Lipid droplets (LDs) are dynamic organelles central to cellular lipid homeostasis. Emerging evidence implicates LDs in Alzheimer's disease (AD) pathogenesis, though their cell-type-specific roles remain poorly defined. Here, we investigated the effects of amyloid-beta oligomers (AβOs) on LDs accumulation, oxidative stress, and inflammatory activation in primary astrocytes and neurons. We found that AβOs selectively triggered robust LDs formation in astrocytes, accompanied by significant increases in triglyceride (TG) and cholesterol (TC) content, and upregulation of the LD-associated protein perilipin 2 (PLIN2). Furthermore, AβOs induced pronounced oxidative stress, evidenced by elevated Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), and promoted inflammatory activation via increased secretion of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) in astrocytes. By contrast, neurons showed no significant changes in lipid metabolism, oxidative stress, or inflammatory responses under identical treatment conditions. Our results underscore the central role of astrocytes in AβO-induced metabolic and inflammatory dysregulation, revealing a cell-type-specific vulnerability with potential implications for AD pathogenesis. These in vitro findings provide a mechanistic basis for lipid-focused therapeutic strategies, pending further in vivo validation.

• High adipocyte infiltration in the tumor microenvironment (TME) is related to significantly increased median overall survival and lower total tumor mutational burden in pancreatic ductal adenocarcinoma (PDAC). • Adipocyte infiltration in the TME facilitates abundant cytokine infiltration and is positively associated with anticancer immune signatures in PDAC. • Adipocytes elicit increased CD8+ T-cell infiltration and potent antitumor activity in transplantation tumor model of PDAC. • We explored the function of adipocytes infiltrating in the TME innovatively and it provides a new perspective on the activation of immune microenvironment in PDAC.

Aims: To analyze the effect of APOE ε4 on fluid biomarkers and the correlations between blood molecules and CSF biomarkers in AD patients.Methods: This study enrolled 575 AD patients, 131 patients with non‐AD dementia, and 112 cognitively normal (CN) participants, and AD patients were divided into APOE ε4 carriers and non‐carriers. Cerebrospinal fluid (CSF) biomarkers and blood‐derived biomolecules were compared between AD and CN groups, between non‐AD dementia and CN groups, as well as within APOE ε4 subgroups of AD patients. Utilizing Spearman's correlation analysis and quantile regression analysis, the relationships between blood‐derived biomolecules and CSF biomarkers were analyzed in APOE ε4 carriers and non‐carriers.Results: The levels of CSF biomarkers and blood molecules exhibited significant differences between the AD and CN groups, including Aβ42, t‐tau, p‐tau 181, high‐density lipoprotein, low‐density lipoprotein (LDL), and uric acid. In AD patients, APOE ε4 carriers had increased levels of CSF t‐tau, p‐tau 181, and plasma LDL. In the correlation and regression analyses, the negative relationships between plasma TG and t‐tau, between plasma TG and p‐tau 181 levels, as well as the positive relationship between serum IgA and CSF Aβ42, were observed significantly in APOE ε4+ AD groups, but not in APOE ε4− AD group.Conclusion: APOE ε4 is associated with accelerated progression of AD pathology. The blood‐derived biomolecules correlated with CSF biomarkers in APOE ε4 carriers are related to neuroinflammation and lipid metabolism, which may indicate the role of APOE ε4 in AD pathophysiology and offer insights for diagnostic and therapeutic strategies for AD.Trial Registration: ClinicalTrials.gov identifier: NCT03653156