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Maria, N. S.

Publications and source records attributed to Maria, N. S..

2 recordsLinked to original sources
bioRxiv2026

Induction of ferroptotic and amyloidogenic signatures linked to Alzheimers disease by chemically distinct air pollutants

Air pollution (AirP) exposure is associated with increased Alzheimers disease (AD) risk, yet AirP is chemically heterogeneous, complicating identification of shared pathogenic drivers. We examined acute cortical responses to two metal-rich AirP sources, diesel exhaust particles (DEP) and World Trade Center (WTC) dust, and compared them to woodsmoke (WS), a particulate exposure with low metal content. DEP and WTC elicited highly convergent transcriptional responses, sharing over 1200 differentially expressed genes linked to inflammation, ferroptosis, neuronal remodeling, and amyloid processing. These changes were accompanied by impaired antioxidant activity and increased lipid peroxidation within lipid rafts, a membrane microdomain critical for amyloid processing, resulting in increased A{beta} generation. In contrast, WS produced a distinct transcriptional signature and failed to induce ferroptotic priming or lipid peroxidation, consistent with its low metal composition. Together, these findings implicate metals as a shared driver linking diverse AirP exposures to amyloidogenic vulnerability and elevated AD risk. Graphical AbstractAcute AirP exposure converges on ferroptotic priming, amyloidogenic processing, and white-matter vulnerability. Acute exposure to metal-rich AirP, such as DEP or WTC introduces redox-active metals and particulate matter that promote lipid peroxidation, amyloidogenesis, and altered transcriptional regulation in the brain. AirP exposure engages xenobiotic metabolism pathways (AhR/ARNT), activates iron and heme handling through ferritinophagy (NCOA4) and heme oxygenase activity (HMOX1), and blunts lipid peroxide detoxification systems, including glutathione peroxidase 4 (GPx4), ferroptosis suppressor protein 1 (FSP1), and glutathione (GSH) synthesis. These changes promote ferroptotic priming and lipid raft oxidation, facilitating amyloid precursor protein (APP) processing by secretases (ADAM10, BACE1, {gamma}-secretase) and increasing amyloid-{beta} (A{beta}) generation. In parallel, transcriptional and cell-state remodeling involving neuronal and oligodendrocyte responses contribute to selective white-matter vulnerability, particularly within the corpus callosum. Together, these pathways provide a mechanistic framework linking acute AirP exposure to convergent oxidative, amyloidogenic, and microstructural changes relevant to Alzheimers disease pathology. O_FIG O_LINKSMALLFIG WIDTH=197 HEIGHT=200 SRC="FIGDIR/small/696601v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@3a22dcorg.highwire.dtl.DTLVardef@c6ae26org.highwire.dtl.DTLVardef@1d3412forg.highwire.dtl.DTLVardef@5cb011_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗
bioRxiv2020

Microvascular Injury in Mild Traumatic Brain Injury Accelerates Alzheimer-like Pathogenesis in Mice

IntroductionTraumatic brain injury (TBI) is considered as the most robust environmental risk factor for Alzheimers disease (AD). Besides direct neuronal injury and neuroinflammation, vascular impairment is also a hallmark event of the pathological cascade after TBI. However, the vascular connection between TBI and subsequent AD pathogenesis remains underexplored. MethodsWe established a closed-head mild TBI (mTBI) model in mice with controlled cortical impact, and examined the time courses of microvascular injury, blood-brain barrier (BBB) dysfunction, gliosis and motor function impairment in wild type C57BL/6 mice. We also determined the brain clearance of {beta}-amyloid, as well as amyloid pathology and cognitive functions after mTBI in the 5xFAD mouse model of AD. ResultsmTBI induced microvascular injury with BBB breakdown, pericyte loss and cerebral blood flow reduction in mice, which preceded gliosis. mTBI also impaired brain amyloid clearance via the vascular pathways. More importantly, mTBI accelerated amyloid pathology and cognitive impairment in the 5xFAD mice. DiscussionOur data demonstrated that microvascular injury plays a key role in the pathogenesis of AD after mTBI. Therefore, restoring vascular functions might be beneficial for patients with mTBI, and potentially reduce the risk of developing AD.

neuroscience↗