👤 Julia R Bacci

Depressive symptoms are common in older adults and have been associated with the risk of Alzheimer's disease/Alzheimer's disease and related dementias (AD/ADRD), but the mechanisms and biomarkers underlying this association remain unclear. We included baseline data from 11,947 non-demented adults aged ≥ 70 years at enrollment in the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial. Linear regressions were used to examine cross-sectional associations between AD/ADRD blood-based biomarkers (BBMs) and baseline depressive symptoms. Interactions between sex or apolipoprotein E (APOE) ε4 carrier status and BBMs were examined. Higher glial fibrillary acidic protein (GFAP) was associated with higher depressive symptoms. We did not observe an association between amyloid beta 42/40 ratio, phosphorylated tau181, or neurofilament light chain with depressive symptoms; interactions between sex or APOE ε4 with depressive symptoms were not significant. In this large, community-based cohort of older adults, plasma GFAP was associated with greater depressive symptoms. Plasma glial fibrillary acidic protein was associated with depressive symptoms. Neuroinflammation may underlie depressive symptoms in this group. Future research is needed to examine sex differences in this association. Show less

Triple-negative breast cancer (TNBC) has limited therapeutic options, is highly metastatic and characterized by early recurrence. Lipid metabolism is generally deregulated in TNBC and might reveal vulnerabilities to be targeted or used as biomarkers with clinical value. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation which is facilitated by the presence of polyunsaturated fatty acids (PUFA). Here we identify fatty acid desaturases 1 and 2 (FADS1/2), which are responsible for PUFA biosynthesis, to be highly expressed in a subset of TNBC with a poorer prognosis. Lipidomic analysis, coupled with functional metabolic assays, showed that FADS1/2 high-expressing TNBC are susceptible to ferroptosis-inducing agents and that targeting FADS1/2 by both genetic interference and pharmacological approach renders those tumors ferroptosis-resistant while unbalancing PUFA/MUFA ratio by the supplementation of exogenous PUFA sensitizes resistant tumors to ferroptosis induction. Last, inhibiting lipid droplet (LD) formation and turnover suppresses the buffering capacity of LD and potentiates iron-dependent cell death. These findings have been validated in vitro and in vivo in mouse- and human-derived clinically relevant models and in a retrospective cohort of TNBC patients. Show less