Molecular Psychiatry最新文献

{"title":"Directing negative emotional states through parallel genetically-distinct basolateral amygdala pathways to ventral striatum subregions","authors":"Sarah E. Sniffen, Sang Eun Ryu, Milayna M. Kokoska, Janardhan Bhattarai, Yingqi Wang, Ellyse R. Thomas, Graylin M. Skates, Natalie L. Johnson, Andy A. Chavez, Sophia R. Iaconis, Emma Janke, Yun-Feng Zhang, Minghong Ma, Daniel W. Wesson","doi":"10.1038/s41380-025-03075-0","DOIUrl":"https://doi.org/10.1038/s41380-025-03075-0","url":null,"abstract":"<p>Distinct basolateral amygdala (BLA) cell populations influence emotions in manners thought important for anxiety and anxiety disorders. The BLA contains numerous cell types which can broadcast information into structures that may elicit changes in emotional states and behaviors. BLA excitatory neurons can be divided into two main classes, one of which expresses <i>Ppp1r1b</i> (encoding protein phosphatase 1 regulatory inhibitor subunit 1B) which is downstream of the genes encoding the D1 and D2 dopamine receptors (<i>Drd1</i> and <i>Drd2</i> respectively). The role of <i>Drd1+</i> or <i>Drd2</i>+ BLA neurons in learned and unlearned emotional responses is unknown. Here, we identified that the <i>Drd1</i>+ and <i>Drd2</i>+ BLA neuron populations form two parallel pathways for communication with the ventral striatum. These neurons arise from the basal nucleus of the BLA, innervate the entire space of the ventral striatum, and are capable of exciting ventral striatum neurons. Further, through two separate behavioral assays, we found that the <i>Drd1</i>+ and <i>Drd2</i>+ parallel pathways distinctly influence both learned and unlearned emotional states when they are activated or suppressed and do so depending upon where they synapse in the ventral striatum – with unique contributions of <i>Drd1</i>+ and <i>Drd2</i>+ circuitry on negative emotional states. Overall, these results contribute to a model whereby parallel, genetically-distinct BLA to ventral striatum circuits inform emotional states in a projection-specific manner.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"37 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"White matter disconnection in acquired criminality","authors":"Isaiah Kletenik, Christopher M. Filley, Alexander L. Cohen, William Drew, Patricia S. Churchland, R. Ryan Darby, Michael D. Fox","doi":"10.1038/s41380-025-03076-z","DOIUrl":"https://doi.org/10.1038/s41380-025-03076-z","url":null,"abstract":"<p>Structural brain imaging is increasingly introduced as evidence in criminal trials. A key imaging abnormality identified in criminal populations is alteration to the right uncinate fasciculus but it remains unclear whether these changes play a causal role in criminal behavior. Lesion studies of acquired criminality offer the opportunity to assess the causal role of focal disruption of specific white matter connections in criminal behavior. We studied lesion locations of focal brain damage associated with new onset criminal behavior compared to lesions associated with 21 diverse neuropsychiatric symptoms. First, we analyzed the intersection of lesion locations with an atlas-based right uncinate fasciculus. Second, we assessed the intersection of lesion locations with all white matter tracts from this atlas. Third, we performed a connectome-based analysis of all possible white matter connections with each lesion location, without a priori assumptions regarding specific tracts. We repeated all analyses limited to subjects who committed violent crimes. Lesions associated with criminality intersected the right uncinate more than lesions associated with other neuropsychiatric symptoms (<i>p</i> = 4.78 × 10⁻⁸). Compared to other tracts, the right uncinate fasciculus was the tract most strongly associated with lesion-induced criminality followed by the forceps minor. An unbiased connectome-based analysis confirmed these findings. Among subjects who committed violent crimes the right uncinate was the key tract identified. Lesions associated with criminality intersect the right uncinate fasciculus more than other lesions and more than other white matter tracts. Damage to the right uncinate may play a causal role in criminal behavior, especially violent crime.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"9 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of brain white matter and social cognition in schizophrenia and schizotypal personality disorder using neurite orientation dispersion and density imaging","authors":"Philip R. Szeszko, Mary Kowalchyk, King-Wai Chu, Sana Aladin, Elen-Sarrah Dolgopolskaia, Sabrina Ng, Sean Hollander, M. Mercedes Perez-Rodriguez, Margaret M. McClure, René S. Kahn, Chi C. Chan, M. Mehmet Haznedar, Kim E. Goldstein, Lazar Fleysher, Erin A. Hazlett","doi":"10.1038/s41380-025-03074-1","DOIUrl":"https://doi.org/10.1038/s41380-025-03074-1","url":null,"abstract":"<p>Schizotypal personality disorder (SPD) is biologically and phenotypically similar to schizophrenia, but without frank psychosis and a general pattern of attenuated brain abnormalities. No studies have investigated the brain white matter in schizophrenia and SPD using neurite orientation dispersion density imaging (NODDI) to distinguish between intracellular vs. extracellular alterations to elucidate neurobiological mechanisms of resilience in the schizophrenia spectrum. In this study we used diffusion tensor imaging and NODDI to investigate putative white matter abnormalities common to schizophrenia (n = 42) and SPD (n = 31) compared to healthy controls (n = 40) and their relationship to social cognition. Individuals with schizophrenia had lower fractional anisotropy (FA) within the inferior fronto-occipital fasciculus and splenium of the corpus callosum compared to healthy controls. The SPD group had FA in these same regions that was intermediate to and significantly different from both groups. Group differences in FA could be attributed specifically to alterations in extracellular fiber coherence in contrast to intracellular neurite density. Lower FA was associated with worse ability to infer sarcasm both in the SPD and schizophrenia groups. These findings implicate attenuated (sparing of) putative white matter abnormalities in SPD in the same brain regions as schizophrenia and comparable structure-function relations in these patient groups. The finding that group differences in FA were driven by alterations in the orientational coherence of neurites suggests that it could serve as an intermediate phenotype in future diffusion imaging studies in the schizophrenia spectrum.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"14 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Dissociable effects of psilocybin and escitalopram for depression on processing of musical surprises.","authors":"Rebecca Harding, Neomi Singer, Matthew B Wall, Talma Hendler, David Erritzoe, David Nutt, Robin Carhart-Harris, Leor Roseman","doi":"10.1038/s41380-025-03066-1","DOIUrl":"https://doi.org/10.1038/s41380-025-03066-1","url":null,"abstract":"","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentially expressed transcripts associated with depressive symptoms during pregnancy and postpartum","authors":"Richelle D. Björvang, Maria Vrettou, Xabier Bujanda Cundin, Eugenio Del Prete, Joëlle Rüegg, Susanne Lager, Diego di Bernardo, Erika Comasco, Alkistis Skalkidou","doi":"10.1038/s41380-025-03068-z","DOIUrl":"https://doi.org/10.1038/s41380-025-03068-z","url":null,"abstract":"<p>Peripartum depression can have severe impact on the mother’s and the infant’s health. Yet, its biological underpinnings are largely unknown. The present study sought to identify transcriptomic signatures of depressive symptoms during pregnancy and postpartum. Blood samples were collected during late pregnancy or early postpartum for mRNA isolation and sequencing, while depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Based on the timepoint when the samples were collected, differentially expressed genes (DEGs) were identified by (1) comparing mRNA levels between the depression symptom trajectory groups, and (2) correlating with EPDS scores. DEGs for samples collected during late pregnancy, but not postpartum, were associated with depressive symptoms occurring only during pregnancy or persisting postpartum, compared with controls. There were 16 upregulated and 109 downregulated DEGs significantly associated with EPDS score at week 32 among samples collected during late pregnancy. Gene Set Enrichment Analysis identified immune response and cell motility as processes linked to these DEGs. Hypothesis-based analysis on previously identified postpartum depressive symptoms-related DEGs replicated a positive association between expression of immune-related genes <i>ISG15</i> and <i>RSAD2</i> with postpartum-onset depressive symptoms, both in samples taken during late pregnancy and postpartum. The present findings point to transcriptomic signatures associated with peripartum depressive symptoms, mostly related to immune system dysregulation.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"54 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic social isolation-unpredictable stress induces early-onset cognitive deficits and exacerbates Aβ accumulation in the 5xFAD mouse model of Alzheimer’s disease","authors":"Yun Lei, Jayvon Nougaisse, Maryam Malek, Miskatul M. Mishu, Yu Bai, Kirstyn Denney, Quansheng Du, Alexis M. Stranahan, Jacob C. Garza, Xin-Yun Lu","doi":"10.1038/s41380-025-03067-0","DOIUrl":"https://doi.org/10.1038/s41380-025-03067-0","url":null,"abstract":"<p>Aging and genetic predisposition are the primary risk factors for Alzheimer’s disease (AD), while chronic stress represents a modifiable risk factor that can accelerate aging and drive AD progression. However, the complex interplay between aging, chronic stress and genetic underpinnings in AD pathogenesis remains poorly understood. Notably, cognitive phenotyping in AD mouse models has yielded inconsistent results. In this study, we characterized the age-dependent trajectory of phenotypes in 5xFAD mice on a congenic C57BL/6 J background. These mice harbor five familial AD (FAD)-related mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes. Aβ plaque deposition was detected in specific brain regions by 4 months of age, but cognitive performance remained intact at this stage. However, by 8–9 months, these mice developed impairments in spatial working memory, novel object recognition memory, and social recognition memory. By 11 months, they also showed metabolic alterations, including lower body weight, higher energy expenditure and increased locomotor activity. Furthermore, after 10 days of chronic social isolation-unpredictable stress, 4-month-old 5xFAD mice exhibited cognitive deficits, accompanied by increased Aβ accumulation in the medial prefrontal cortex, hippocampus, and entorhinal cortex. In contrast, age- and sex-matched wild-type littermate controls subjected to the same stress paradigm showed no significant cognitive changes. These observations suggest that Aβ deposition increases stress vulnerability in 5xFAD mice. We conclude that the phenotypic expression of AD-related gene mutations, including pathological changes and cognitive decline, progresses with age and can be induced by chronic psychological stress, underscoring the interactive effects of stress, aging, and genetic vulnerability on disease onset and severity.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"36 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose restriction induces degeneration of neurons with mitochondrial DNA depletion by altering ER-mitochondria calcium transfer","authors":"Lingyan Zhou, Feixiang Bao, Jiajun Zheng, Yingzhe Ding, Jiahui Xiao, Jian Zhang, Yongpeng Qin, Liang Yang, Yi Wu, Qi Meng, Manjiao Lu, Qi Long, Lingli Hu, Chong Li, Haitao Wang, Shijuan Huang, Linpeng Li, Junwei Wang, Wuming Wang, Gang Lu, Wai-Yee Chan, Dajiang Qin, Gong Chen, Xingguo Liu","doi":"10.1038/s41380-025-03069-y","DOIUrl":"https://doi.org/10.1038/s41380-025-03069-y","url":null,"abstract":"<p>Mitochondrial DNA (mtDNA) mutations and/or depletion are implicated in epilepsy and many neurodegenerative diseases. However, systematic investigation into how mtDNA alterations relate to epilepsy and neural degeneration is needed. Here, we established a mouse model in which mtDNA depletion is induced by the Herpes Simplex Virus Type 1 (HSV-1) protein UL12.5 in the brain led to an epileptic phenotype characterized by abnormal electroencephalography (EEG) patterns and increased neural excitability in hippocampus. We also found that UL12.5 mediated mtDNA depletion in neurons in vitro (rho⁻) causes epilepsy–like abnormal EEG. Caloric restriction (CR) or glucose restriction (GR) is a strategy proven to reduce epileptic activity, however GR mimetic 2-deoxy-D-glucose (2-DG), induced degeneration in mtDNA depleted neurons. Mechanistically, mtDNA depletion increased mitochondria-endoplasmic reticulum (ER) contacts, facilitating GR-induced mitochondrial calcium overload. Rho⁻ neurons did not show changes in mitochondrial motility or membrane potential. Our study revealed an unexpected axis of mtDNA depletion, ER-mitochondrial contacts, and calcium overload in the rho⁻ neuron model. Fasting-induced GR causes early motor dysfunction, accelerates epilepsy progression, and worsens neurodegeneration in UL12.5 mice. Importantly, the IP3R inhibitor 2-APB blocks the neurodegeneration induced by fasting. This is the first description of animal and neuronal models of mitochondrial epilepsy. Our findings with these models suggest that GR may not be a viable clinical intervention in patients with mtDNA depletion.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"134 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical AI application in psychiatry: historical review and future directions","authors":"Jie Sun, Tangsheng Lu, Xuexiao Shao, Ying Han, Yu Xia, Yongbo Zheng, Yongxiang Wang, Xinmin Li, Arun Ravindran, Lizhou Fan, Yin Fang, Xiujun Zhang, Nisha Ravindran, Yumei Wang, Xiaoxing Liu, Lin Lu","doi":"10.1038/s41380-025-03072-3","DOIUrl":"https://doi.org/10.1038/s41380-025-03072-3","url":null,"abstract":"<p>The integration of artificial intelligence (AI) in mental healthcare holds promise for enhancing diagnostic precision, treatment efficacy, and personalized care. Despite AI’s potential to analyze vast datasets and identify subtle patterns, its clinical adoption in psychiatry remains limited. This review critically examines the emerging role of AI in psychiatry, elucidating its utility, challenges, and implications for clinical practice. Through an extensive analysis of the existing literature and empirical evidence, we seek to inform psychiatric stakeholders about both opportunities and obstacles that are presented by AI. We evaluate AI’s potential to improve diagnostic accuracy, prognostic performance, and therapeutic interventions. Our pragmatic approach bridges the gap between theoretical advancements and practical implementation, providing valuable insights and actionable recommendations for psychiatric professionals. This article highlights the supportive role of AI, advocating for its judicious integration to enhance patient outcomes while maintaining the human-centric essence of psychiatric practice. By addressing these challenges and fostering collaboration, AI can significantly advance mental healthcare, reduce clinical burdens, and improve patient outcomes.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"11 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144202143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating genome-wide information and wearable device data to explore the link of anxiety and antidepressants with pulse rate variability.","authors":"Eleni Friligkou, Dora Koller, Gita A Pathak, Edward J Miller, Rachel Lampert, Murray B Stein, Renato Polimanti","doi":"10.1038/s41380-024-02836-7","DOIUrl":"10.1038/s41380-024-02836-7","url":null,"abstract":"<p><p>This study explores the genetic and epidemiologic correlates of long-term photoplethysmography-derived pulse rate variability (PRV) measurements with anxiety disorders. Individuals with whole-genome sequencing, Fitbit, and electronic health record data (N = 920; 61,333 data points) were selected from the All of Us Research Program. Anxiety polygenic risk scores (PRS) were derived with PRS-CS after meta-analyzing anxiety genome-wide association studies from three major cohorts- UK Biobank, FinnGen, and the Million Veterans Program (N_Total =364,550). PRV was estimated as the standard deviation of average five-minute pulse wave intervals over full 24-hour pulse rate measurements (SDANN). Antidepressant exposure was defined as an active antidepressant prescription at the time of the PRV measurement in the EHR. Anxiety PRS and antidepressant use were tested for association with daily SDANN. The potential causal effect of anxiety on PRV was assessed with one-sample Mendelian randomization (MR). Anxiety PRS was independently associated with reduced SDANN (beta = -0.08; p = 0.003). Of the eight antidepressant medications and four classes tested, venlafaxine (beta = -0.12, p = 0.002) and bupropion (beta = -0.071, p = 0.01), tricyclic antidepressants (beta = -0.177, p = 0.0008), selective serotonin reuptake inhibitors (beta = -0.069; p = 0.0008) and serotonin and norepinephrine reuptake inhibitors (beta = -0.16; p = 2×10^-6) were associated with decreased SDANN. One-sample MR indicated an inverse effect of anxiety on SDANN (beta = -2.22, p = 0.03). Anxiety and antidepressants are independently associated with decreased PRV, and anxiety appears to exert a causal effect on reduced PRV. Those observational findings provide insights into the impact of anxiety on PRV.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":"2309-2315"},"PeriodicalIF":9.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pathogenic APP N-terminal Val225Ala mutation alters tau protein liquid-liquid phase separation and exacerbates synaptic damage.","authors":"Jiang Chen, Song Li, Fengning Zhang, Junsheng Chen, Chuanbin Cai, Yi Guo, Zhifeng Lei, Ling-Hui Zeng, Dan Zi, Yong Shen, Jun Tan","doi":"10.1038/s41380-024-02837-6","DOIUrl":"10.1038/s41380-024-02837-6","url":null,"abstract":"<p><p>Amyloid precursor protein (APP) is predominantly located in synapses of neurons and its mutations have been well recognized as the most important genetic causal factor for the familial Alzheimer's disease (AD). While most disease-causal mutations of APP occur within the Aβ-coding region or immediately proximal, the pathological impacts of mutations in the N-terminus of APP protein, which remote from the Aβ sequence, on neuron and synapse are still largely unknown. It was recently reported a pathogenic APP N-terminal Val225Ala mutation (APP_V225A) with clinically featuring progressive dementia and typical AD pathologies in brain. In our present study, we further found that APP_V225A mutation alters the N-terminal structure of APP, which enhances its binding affinity to tau protein and significantly increases APP-mediated endocytosis. Consequently, APP_V225A promotes the uptake of extracellular tau into SH-SY5Y cells, further linking the structural change in APP to intracellular tau accumulation. In addition, APP_V225A also notably alters the liquid-liquid phase separation (LLPS) of intracellular tau and intensified tau phosphorylation and aggregation in SH-SY5Y cells. Moreover, APP_V225A promote AD-like tau pathology and synaptic damages in human induced pluripotent stem cells (hiPSCs)-derived neural progenitor cells and neurons, as well as in hiPSCs-derived human brain organoids and mouse brain, which can be ameliorated by tau knockdown. Proximity labeling identified several key APP_V225A-interacting proteins, including HS3ST3A1, which was shown to directly regulate tau LLPS and phosphorylation. These findings nicely build on our previous work on roles for APP in tau-related pathological phenotypes and further highlight the involvement of N-terminal APP as the key region for both amyloidopathy and tauopathy, two aspects of AD pathogenesis and progression. Our study may also provide a theoretical breakthrough for AD therapy and highlight the important hub roles of APP and making previously neglected N-terminal APP as a potential target for the discovery of novel disease-modifying therapeutic agents against AD, holding significant scientific values and clinical promise.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":"2316-2334"},"PeriodicalIF":9.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}