Victoria Soto Linan , Véronique Rioux , Modesto Peralta III , Nicolas Dupré , Marc Hébert , Martin Lévesque
{"title":"Early detection of Parkinson's disease: Retinal functional impairments as potential biomarkers","authors":"Victoria Soto Linan , Véronique Rioux , Modesto Peralta III , Nicolas Dupré , Marc Hébert , Martin Lévesque","doi":"10.1016/j.nbd.2025.106872","DOIUrl":"10.1016/j.nbd.2025.106872","url":null,"abstract":"<div><h3>Background</h3><div>Parkinson's disease is typically diagnosed after substantial neurodegeneration despite early non-motor symptoms manifesting decades earlier. These changes offer a promising avenue for diagnostic exploration, especially within the eye, which has been proposed as a “window to the brain.”</div></div><div><h3>Objective</h3><div>The aim was to identify biomarkers by validating the use of electroretinography, a non-invasive technique, to detect early retinal function anomalies reflecting central dysfunction.</div></div><div><h3>Methods</h3><div>Homozygous M83 transgenic mice (<em>n</em> = 10 males, 11 females), overexpressing human A53T α-synuclein, underwent behavioral tests and electroretinography measurements. Histological evaluation was performed at four months to analyze synucleinopathies and neurodegeneration. Electroretinography was also conducted with idiopathic PD patients (mean age 63.35 ± 7.73; disease duration 4.15 ± 2.06; H&Y score 2.07 ± 0.59; <em>n</em> = 12 males, 8 females) and healthy age-matched controls (mean age 61.65 ± 8.39; <em>n</em> = 9 males, 11 females).</div></div><div><h3>Results</h3><div>Rodent electroretinography revealed reduced photopic b-wave, PhNR b-wave, and PhNR-wave amplitudes at two and four months, particularly in females, indicating bipolar and retinal ganglion cell impairment. Based on retinal histological assessment, these changes might arise from α-synuclein pathology occurring in outer retinal layers. Likewise, the scotopic b-wave and PhNR waveform were similarly impaired in female participants with Parkinson's disease. The scotopic oscillatory potentials isolated further identified an attenuated amacrine cell output in females.</div></div><div><h3>Conclusions</h3><div>Findings from both mice and human cohorts indicate that retinal functional impairments can be detected early in the progression of Parkinson's disease, particularly among females. These tools show promise in facilitating early diagnosis, disease monitoring, therapeutic intervention, and ultimately enhancing patient outcomes.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"208 ","pages":"Article 106872"},"PeriodicalIF":5.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shaojun Li , Guanfeng Zeng , Chunmei Pang , Jie Li , Li Wu, Ming Luo, Zhihua Qiu, Yongjun Jiang
{"title":"Single-cell and spatial transcriptomics analysis reveals that Pros1+ oligodendrocytes are involved in endogenous neuroprotection after brainstem stroke","authors":"Shaojun Li , Guanfeng Zeng , Chunmei Pang , Jie Li , Li Wu, Ming Luo, Zhihua Qiu, Yongjun Jiang","doi":"10.1016/j.nbd.2025.106855","DOIUrl":"10.1016/j.nbd.2025.106855","url":null,"abstract":"<div><h3>Background</h3><div>Brainstem stroke accounts only 7–10 % of all ischemic stroke while it had more morbidity and mortality. As the predominant cellular component of nerve tracts, oligodendrocytes might provide some neuroprotection against ischemic injury in the context of brainstem stroke, but the underlying mechanism remains unclear.</div></div><div><h3>Method</h3><div>A mouse model of brainstem stroke was established, and single-cell RNA sequencing and spatial transcriptomic sequencing analysis were performed to elucidate the phenotype of oligodendrocytes within this context.</div></div><div><h3>Results</h3><div>Loss of oligodendrocytes led to neurological impairment following brainstem stroke, and subsequent proliferation of oligodendrocytes was observed. We identified a subcluster of <em>Pros1</em><sup><em>+</em></sup> oligodendrocytes, designated OLG8 cells. These cells increased in number after brainstem stroke and were enriched around the peri-infarct zone. OLG8 cells were derived from oligodendrocyte progenitor cells, and this process was found to be regulated by Myo1e. We found that OLG8 cells protected interneurons. Notably, the overexpression of Myo1e within OLG8 cells led to a marked reduction in infarct volume while simultaneously improving the recovery of neurological function.</div></div><div><h3>Conclusion</h3><div>In conclusion, we identified a novel cell subcluster, OLG8 cells, in the context of brainstem stroke, and found that overexpression of Myo1e alleviated ischemic injury by facilitating the differentiation of OLG8 cells. Our study provided insight into the mechanism of brainstem stroke.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"208 ","pages":"Article 106855"},"PeriodicalIF":5.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Margaux Lebouc , Léa Bonamy , Thibault Dhellemmes , Jakob Scharnholz , Quentin Richard , Gilles Courtand , Alexandre Brochard , Frédéric Martins , Marc Landry , Jérôme Baufreton , Maurice Garret
{"title":"Developmental alterations of indirect-pathway medium spiny neurons in mouse models of Huntington's disease","authors":"Margaux Lebouc , Léa Bonamy , Thibault Dhellemmes , Jakob Scharnholz , Quentin Richard , Gilles Courtand , Alexandre Brochard , Frédéric Martins , Marc Landry , Jérôme Baufreton , Maurice Garret","doi":"10.1016/j.nbd.2025.106874","DOIUrl":"10.1016/j.nbd.2025.106874","url":null,"abstract":"<div><div>Huntington's disease (HD) is a complex neurodegenerative disorder with cognitive and motor symptoms that typically manifest in adulthood. However, embryonic brain development impairments leading to cortical defects in HD mutation carriers has been shown recently supporting a neurodevelopmental component in HD. Despite HD is primarily recognized as a striatal pathology, developmental alterations in this structure, particularly during the early postnatal period, remain poorly understood. To fill this gap, we examined striatal development in newborn R6/1 mice. We found that D2 receptor-expressing indirect-pathway medium spiny neurons (D2-MSNs) present in the matrix striatal compartment undergo early morphological and electrophysiological maturation. Altered electrophysiological properties were also observed in newborn CAG140 mice. Additionally, we also observed a D2-MSN-selective reduction in glutamatergic cortico-striatal transmission at the beginning of the second postnatal week as well as a reduced projection of D2-MSNs onto the GPe at birth in R6/1 mice. All these alterations were transient with the circuit normalizing after the second postnatal week. These results identify a compartment- and cell-type specific defect in D2-MSNs maturation, which can contribute in their latter vulnerability, as this cell-type is the first to degenerate in HD during adulthood.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"208 ","pages":"Article 106874"},"PeriodicalIF":5.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Qiong Fu , Yu Zheng , Zhuo Li Li , Xin Yi Huang , Xiao Wan Wang , Mai Yin Cui , Yun Qi Zhang , Bing Rui Gao , Chan Zhang , Xiao Xiao Fan , Yong Jian , Bai Hui Chen
{"title":"SARM1 deletion inhibits astrogliosis and BBB damage through Jagged-1/Notch-1/NF-κB signaling to improve neurological function after ischemic stroke","authors":"Yan Qiong Fu , Yu Zheng , Zhuo Li Li , Xin Yi Huang , Xiao Wan Wang , Mai Yin Cui , Yun Qi Zhang , Bing Rui Gao , Chan Zhang , Xiao Xiao Fan , Yong Jian , Bai Hui Chen","doi":"10.1016/j.nbd.2025.106873","DOIUrl":"10.1016/j.nbd.2025.106873","url":null,"abstract":"<div><div>Reactive astrogliosis is a critical process in the development of ischemic stroke. However, the precise mechanism by which reactive astrogliosis changes the pathogenesis of ischemic stroke remains elusive. Sterile alpha and TIR motif-containing 1 protein (SARM1) plays a key role in axonal degeneration and is involved in different cell death programs that regulate neuronal survival. The present study investigated the role of SARM1 in regulating reactive astrogliosis and neurological function after stroke in whole-body SARM1 knockout (SARM1<sup>−/−</sup>) mice. SARM1<sup>−/−</sup> mice showed significantly smaller infarction, slighter apoptosis, and fewer neurological function deficits 1–7 days after ischemic injury. Immunohistochemistry, western blot, and real-time PCR analyses revealed that compared with the wild-type (WT) mice, SARM1<sup>−/−</sup> mice exhibited reduced astrocytic proliferation, increased anti-inflammatory astrocytes, decreased glial scar formation in the infarct zone on day 7 after ischemic injury. SARM1 deletion also suppressed cerebral microvascular damage and blood-brain barrier (BBB) injury in ischemic brains. Mechanistically, SARM1 deletion inhibited the stroke-triggered activation of NF-κB signaling and decreased the expression of Jagged-1 and NICD in astrocytes. Overall, these findings provide the first line of evidence for a causative role of SARM1 protein in ischemia-induced reactive astrogliosis and ischemic neurovascular damage.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"208 ","pages":"Article 106873"},"PeriodicalIF":5.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lily E. Takeuchi , Lorraine V. Kalia , Craig A. Simmons
{"title":"Vascular models of Alzheimer's disease: An overview of recent in vitro models of the blood-brain barrier","authors":"Lily E. Takeuchi , Lorraine V. Kalia , Craig A. Simmons","doi":"10.1016/j.nbd.2025.106864","DOIUrl":"10.1016/j.nbd.2025.106864","url":null,"abstract":"<div><div>Alzheimer's disease (AD) remains an overwhelming epidemiologic and economic burden on our healthcare systems, affecting an estimate of 11 % of individuals aged 65 years and older. Increasing evidence of the role of the blood-brain barrier (BBB) in AD pathology lends support to the vascular hypothesis of AD, which posits that damage to cerebral vasculature and impairments to cerebral blood flow are major contributors to neurodegeneration in AD. While the question remains whether the dysfunction of the BBB is the cause or consequence of the disease, understanding of the relationship between vascular pathology and AD is growing increasingly complex, warranting the need for better tools to study vasculature in AD. This review provides an overview of AD models in the context of studying vascular impairments and their relevance in pathology. Specifically, we summarize opportunities in <em>in vitro</em> models, cell sources, and phenotypic observations in sporadic and familial forms of AD. Further, we describe recent advances in generating models which recapitulate <em>in vivo</em> characteristics of the BBB in AD through the use of microfluidics, induced pluripotent stem cells (iPSC), and organoid technologies. Finally, we provide a searchable database of reported cell-based models of pathogenic AD gene variants.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"208 ","pages":"Article 106864"},"PeriodicalIF":5.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Parievsky, Cindy Moore, Talia Kamdjou, Carlos Cepeda, Charles K Meshul, Michael S Levine
{"title":"Corrigendum to \"Differential electrophysiological and morphological alterations of thalamostriatal and corticostriatal projections in the R6/2 mouse model of Huntington's disease\" [Neurobiology of Disease 108 (2017) Pages 29-44].","authors":"Anna Parievsky, Cindy Moore, Talia Kamdjou, Carlos Cepeda, Charles K Meshul, Michael S Levine","doi":"10.1016/j.nbd.2025.106860","DOIUrl":"https://doi.org/10.1016/j.nbd.2025.106860","url":null,"abstract":"","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":" ","pages":"106860"},"PeriodicalIF":5.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lorenzo Pini , Lorenza Brusini , Alessandra Griffa , Federica Cruciani , Gilles Allali , Giovanni B. Frisoni , Maurizio Corbetta , Gloria Menegaz , Ilaria Boscolo Galazzo , for the Alzheimer's Disease Neuroimaging Initiative
{"title":"Functional dynamic network connectivity differentiates biological patterns in the Alzheimer's disease continuum","authors":"Lorenzo Pini , Lorenza Brusini , Alessandra Griffa , Federica Cruciani , Gilles Allali , Giovanni B. Frisoni , Maurizio Corbetta , Gloria Menegaz , Ilaria Boscolo Galazzo , for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1016/j.nbd.2025.106866","DOIUrl":"10.1016/j.nbd.2025.106866","url":null,"abstract":"<div><div>Alzheimer's disease (AD) can be conceptualized as a network-based syndrome. Network alterations are linked to the molecular hallmarks of AD, involving amyloid-beta and tau accumulation, and consecutively neurodegeneration. By combining molecular and resting-state functional magnetic resonance imaging, we assessed whether different biological patterns of AD identified through a data-driven approach matched specific abnormalities in brain dynamic connectivity. We identified three main patient clusters. The first group displayed mild pathological alterations. The second cluster exhibited typical behavioral impairment alongside AD pathology. The third cluster demonstrated similar behavioral impairment but with a divergent tau (low) and neurodegeneration (high) profile. Univariate and multivariate analyses revealed two connectivity patterns encompassing the default mode network and the occipito-temporal cortex, linked respectively with typical and atypical patterns. These results support the key association between macro-scale and molecular alterations. Dynamic connectivity markers can assist in identifying patients with AD-like clinical profiles but with different underlying pathologies.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"208 ","pages":"Article 106866"},"PeriodicalIF":5.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huimin Sun , Caiting Gan , Xingyue Cao , Yongsheng Yuan , Heng Zhang , Chenhui Wan , Jiaxin Shi , Xufeng Wang , Youyong Kong , Tao Feng , Kezhong Zhang
{"title":"Microstructural and functional abnormalities of the locus coeruleus in freezing of gait in Parkinson's disease","authors":"Huimin Sun , Caiting Gan , Xingyue Cao , Yongsheng Yuan , Heng Zhang , Chenhui Wan , Jiaxin Shi , Xufeng Wang , Youyong Kong , Tao Feng , Kezhong Zhang","doi":"10.1016/j.nbd.2025.106868","DOIUrl":"10.1016/j.nbd.2025.106868","url":null,"abstract":"<div><h3>Objective</h3><div>The loss of locus coeruleus (LC)-norepinephrine system may contribute to freezing of gait (FOG) in Parkinson's disease (PD), but free-water (FW) imaging has not been applied to investigate LC microstructural degeneration in FOG. This study was to investigate the role of the LC-norepinephrine system in FOG pathophysiology using FW imaging and resting-state functional magnetic resonance imaging.</div></div><div><h3>Methods</h3><div>FW metrics of LC were analyzed in 52 healthy controls, 79 PD patients without FOG (Non-FOG), and 110 PD patients with FOG (48 “Off-period” FOG and 62 “Levodopa unresponsive” FOG). Correlation between LC FW metrics and clinical scales were assessed. Functional connectivity analysis with LC as the region of interest was performed across groups during medication withdrawal. Structural and functional differences in LC between FOG subgroups and the effects of dopaminergic medication were also explored.</div></div><div><h3>Results</h3><div>FOG patients had increased FW value, FW-corrected mean diffusivity, axial diffusivity, and radial diffusivity in LC, and decreased FW-corrected fractional anisotropy compared to Non-FOG patients and healthy controls. In FOG patients, FW value and FW-corrected mean axial diffusivity were positively correlated with the new FOG questionnaire scores. LC functional connectivity with occipital regions was reduced in FOG patients. No significant differences in LC microstructure or functional connectivity were observed between FOG subgroups during their “OFF” state. In contrast to “Levodopa-unresponsive” FOG patients, oral medication significantly improved LC functional connectivity with occipital regions in “Off-period” FOG patients.</div></div><div><h3>Conclusions</h3><div>LC degeneration may disrupt motor and compensatory network integration, especially in visual-motor pathways, contributing to FOG.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"208 ","pages":"Article 106868"},"PeriodicalIF":5.1,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Costanza Mazzantini , Martina Venturini , Daniele Lana , Gloria Mulas , Clara Santalmasi , Giada Magni , Paola Bruni , Anna Maria Pugliese , Francesca Cencetti , Domenico E. Pellegrini-Giampietro , Elisa Landucci
{"title":"Dual action of sphingosine 1-phosphate pathway in in vitro models of global cerebral ischemia","authors":"Costanza Mazzantini , Martina Venturini , Daniele Lana , Gloria Mulas , Clara Santalmasi , Giada Magni , Paola Bruni , Anna Maria Pugliese , Francesca Cencetti , Domenico E. Pellegrini-Giampietro , Elisa Landucci","doi":"10.1016/j.nbd.2025.106865","DOIUrl":"10.1016/j.nbd.2025.106865","url":null,"abstract":"<div><div>It is well accepted that sphingolipids play an important role in the pathological process of cerebral ischemia. In the present study we have investigated the involvement of sphingosine 1-phosphate (S1P) pathway in two different in vitro models of global ischemia.</div><div>In organotypic hippocampal slices exposed to oxygen and glucose deprivation (OGD) we evaluated the mRNA expression of S1P metabolic enzymes and receptors (S1P<sub>1–5</sub>) by Real Time-PCR. In the same model we investigated the effect of the inhibitor of S1P lyase (SPL), LX2931, the selective antagonists of S1P<sub>2</sub>, JTE-013, and S1P<sub>3</sub>, CAY10444, quantifying the cell death in the CA1 region by propidium iodide fluorescence, and morphological and tissue organization alterations by immunohistochemistry and confocal microscopy. Moreover, we performed extracellular recordings of field excitatory postsynaptic potentials in acute slices exposed to OGD.</div><div>In organotypic slices OGD induced a significant increase of SPL at mRNA level and of S1P<sub>2</sub> and S1P<sub>3</sub> at both mRNA and protein level. The incubation with LX2931, JTE-013 or CAY10444 was able to reduce CA1 damage induced by OGD in organotypic slices and provoked a significant delay of the onset of anoxic depolarization on acute slices. Moreover, S1P<sub>2</sub> and S1P<sub>3</sub> antagonists prevented the increase of TREM2 induced by OGD.</div><div>Our results reveal a dual role of S1P pathway in brain ischemia: intracellular S1P, degraded via SPL, appears to be beneficial whereas signaling via S1P<sub>2</sub> and S1P<sub>3</sub> is detrimental to the disease. These findings support the notion that SPL, S1P<sub>2</sub> and S1P<sub>3</sub> are promising therapeutic targets in brain ischemia.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"208 ","pages":"Article 106865"},"PeriodicalIF":5.1,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Serpente , Giuseppe Delvecchio , Chiara Fenoglio , Lorena Di Consoli , Giulia Giudici , Vittoria Borracci , Emanuela Rotondo , Marina Arcaro , Luca Sacchi , Manuela Pintus , Laura Ghezzi , Adele Ferro , Cecilia Prunas , Antonio Callari , Elisa Scola , Fabio M. Triulzi , Andrea Arighi , Paolo Brambilla , Daniela Galimberti
{"title":"Differential miRNA expression in neural-enriched extracellular vesicles as potential biomarker for frontotemporal dementia and bipolar disorder","authors":"Maria Serpente , Giuseppe Delvecchio , Chiara Fenoglio , Lorena Di Consoli , Giulia Giudici , Vittoria Borracci , Emanuela Rotondo , Marina Arcaro , Luca Sacchi , Manuela Pintus , Laura Ghezzi , Adele Ferro , Cecilia Prunas , Antonio Callari , Elisa Scola , Fabio M. Triulzi , Andrea Arighi , Paolo Brambilla , Daniela Galimberti","doi":"10.1016/j.nbd.2025.106867","DOIUrl":"10.1016/j.nbd.2025.106867","url":null,"abstract":"<div><div>Behavioral variant of Frontotemporal Dementia (bvFTD) and Bipolar Disorder (BD) share overlapping symptoms, complicating diagnosis. BvFTD, especially linked to C9orf72 expansions, often mimics BD, highlighting the need for reliable biomarkers. This study aimed to differentiate bvFTD from BD using miRNA profiles in neural-enriched extracellular vesicles (NEVs). A cohort of 100 subjects was analyzed: 40 bvFTD (20 sporadic, 20 C9orf72 carriers), 40 BD, and 20 healthy controls. NEVs were isolated from plasma and profiled using real-time PCR. Among 754 miRNAs, 11 were significantly deregulated in bvFTD and BD. MiR-152-5p was downregulated in sporadic bvFTD, while let-7b, let-7e, miR-18b, and miR-142-5p were altered in C9orf72 carriers. BD patients showed distinct patterns in miR-331-5p, miR-335, and miR-345 compared to bvFTD. Bioinformatics analyses revealed that let-7e, let-7b, miR-18b, and miR-142-5p share common long non-coding RNA (lncRNA) targets, including XIST, NEAT1, and OIP5-AS1, suggesting their involvement in molecular networks relevant to C9orf72-related bvFTD. These miRNA signatures can differentiate bvFTD from BD, especially in C9orf72-related cases, and offer insights into disease pathways. Further research is needed to validate these findings and explore their clinical application.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"208 ","pages":"Article 106867"},"PeriodicalIF":5.1,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}