Journal of Huntington's disease最新文献

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A systematic review of performance-based functional capacity measures for use in Huntington's disease and evaluation of their suitability for clinical trials. 对亨廷顿氏病的功能测试方法进行系统回顾,并评估其是否适用于临床试验。
IF 2.1
Journal of Huntington's disease Pub Date : 2025-04-03 DOI: 10.1177/18796397251330846
Tayela M Prichard, Cali M Roiboit, Meg E Rankin, Yifat Glikmann-Johnston, Mark F Gordon, Julie C Stout
{"title":"A systematic review of performance-based functional capacity measures for use in Huntington's disease and evaluation of their suitability for clinical trials.","authors":"Tayela M Prichard, Cali M Roiboit, Meg E Rankin, Yifat Glikmann-Johnston, Mark F Gordon, Julie C Stout","doi":"10.1177/18796397251330846","DOIUrl":"https://doi.org/10.1177/18796397251330846","url":null,"abstract":"<p><p>BackgroundHuntington's disease (HD) leads to a decline in functional capacity, affecting daily life tasks. Assessing functional capacity in clinical trials is crucial to evaluate treatment effectiveness and substantiate the clinical meaningfulness of more sensitive and reliable measures. Clinician rating scales are commonly used, but performance-based measures of functional capacity may offer advantages, however, there is no consensus on the suitability of existing performance-based measures for use in HD.ObjectiveWe applied a Consensus-based Standards for the selection of health Measurement INstruments (COSMIN) approach to evaluate the potential suitability of performance-based functional capacity measures for HD clinical trials. We also used criteria developed with expert input to assess these measures.MethodsWe conducted a systematic search of relevant databases and screened 1924 articles for inclusion criteria.ResultsWe included a total of 89 articles on 33 performance-based functional capacity measures. Measures were rated from Very Low to Moderate suitability for use in HD clinical trials. DriveSafe DriveAware and EcoKitchen were the only measures tested in HD participants and were rated as having Moderate and Very Low suitability respectively, highlighting the need for further evaluation. Additionally, the Brief University of California San Diego Performance-based Skills Assessment (UCSD UPSA-B) and the Virtual Reality Functional Capacity Assessment Tool (VRFCAT), were identified as potentially useful, also rated Moderate.ConclusionsMultiple performance-based functional capacity measures show potential for use in patients with HD, pending further investigation.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251330846"},"PeriodicalIF":2.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Emerging roles of microglia and neuroinflammation in Huntington's disease: From pathophysiology to clinical trials.
IF 2.1
Journal of Huntington's disease Pub Date : 2025-03-28 DOI: 10.1177/18796397251330144
Muna Abedrabbo, Pardis Kazemian, Colúm Connolly, Blair R Leavitt
{"title":"Emerging roles of microglia and neuroinflammation in Huntington's disease: From pathophysiology to clinical trials.","authors":"Muna Abedrabbo, Pardis Kazemian, Colúm Connolly, Blair R Leavitt","doi":"10.1177/18796397251330144","DOIUrl":"https://doi.org/10.1177/18796397251330144","url":null,"abstract":"<p><p>Microglia, the resident immune cells of the central nervous system, play a pivotal role in the response to Huntington's disease (HD) pathology. Through both cell-autonomous mechanisms and exposure to external pathogenic stimuli, microglia transition from a resting to an activated state, producing pro-inflammatory cytokines and chemokines that mediate inflammation. While this inflammatory response attempts to have a neuroprotective compensatory effect, chronic microglial activation exacerbates neuroinflammation, neurodegeneration and contributes to disease progression. Evidence from postmortem analyses and neuroimaging studies indicates that activated microglia are present in various stages of HD, correlating with neuronal degeneration and clinical symptoms. Enhanced microglial activation has been identified as an early predictor of disease onset, particularly in premanifest HD, highlighting the potential of targeting microglial pathways for therapeutic interventions. This review explores microglia's dual role in HD pathophysiology, exploring their contributions to both neuroinflammation and neuroprotection. It also examines recent advances in clinical trials aimed at modulating microglial activity, paving the way for novel therapeutic strategies to alter disease progression and improve patient outcomes.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251330144"},"PeriodicalIF":2.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The glymphatic system in Huntington's disease.
IF 2.1
Journal of Huntington's disease Pub Date : 2025-03-28 DOI: 10.1177/18796397251331436
Wenzhen Duan, Yuan Zhou, Hongshuai Liu
{"title":"The glymphatic system in Huntington's disease.","authors":"Wenzhen Duan, Yuan Zhou, Hongshuai Liu","doi":"10.1177/18796397251331436","DOIUrl":"https://doi.org/10.1177/18796397251331436","url":null,"abstract":"<p><p>The glymphatic system, a macroscopic waste clearance network in the brain, plays a vital role in maintaining neuronal health and brain homeostasis. Functionally analogous to the lymphatic system in other organs, the term \"glymphatic\" combines \"glial\" and \"lymphatic.\" This system facilitates the exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF) in the parenchyma, aiding in the removal of soluble proteins and metabolites while distributing essential nutrients and signaling molecules. Its functionality is closely tied to aquaporin 4 (AQP4) water channels, located primarily on astrocytic endfeet, which mediate water movement between the CSF and ISF. Proper glymphatic function relies on the cellular distribution of AQP4 channels and its astroglial endfeet polarization. Emerging evidence links glymphatic dysfunction to several neurodegenerative disorders, including Huntington's disease (HD). Understanding the role of the glymphatic system in HD pathogenesis could provide novel insights into disease pathogenesis and new therapeutic approaches. This review examines the connection between glymphatic dysfunction and HD, highlighting future research directions and therapeutic advancement for HD. It explores pharmacological interventions and lifestyle modifications aimed at optimizing glymphatic function to improve HD management.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251331436"},"PeriodicalIF":2.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deutetrabenazine treatment outcomes with doses above U.S. Food and Drug Administration maximum approved doses in Huntington's disease chorea: A dual-site analysis.
IF 2.1
Journal of Huntington's disease Pub Date : 2025-03-23 DOI: 10.1177/18796397251323293
Kayla Dodson, Sabrina Livezey, Brittany Denson, Leena Choi, Josh DeClercq, Autumn D Zuckerman, Kayla Johnson
{"title":"Deutetrabenazine treatment outcomes with doses above U.S. Food and Drug Administration maximum approved doses in Huntington's disease chorea: A dual-site analysis.","authors":"Kayla Dodson, Sabrina Livezey, Brittany Denson, Leena Choi, Josh DeClercq, Autumn D Zuckerman, Kayla Johnson","doi":"10.1177/18796397251323293","DOIUrl":"https://doi.org/10.1177/18796397251323293","url":null,"abstract":"<p><p>BackgroundDeutetrabenazine, a vesicular monoamine transporter 2 inhibitor, is one of few treatment options available for Huntington's disease (HD) chorea. There is limited data describing clinical experience with deutetrabenazine doses >48 mg daily.ObjectiveDescribe treatment outcomes for deutetrabenazine >48 mg daily.MethodsA dual site retrospective cohort study of patients on deutetrabenazine titrated to doses >48 mg/day for HD chorea from April 2017 through December 2021 was conducted. Patients using concomitant strong CYP2D6 inhibitors at time of deutetrabenazine initiation, those who became deceased or lost to follow-up within six months of dose increase above 48 mg/day, or previously enrolled in a study on >48 mg daily and moving to commercial product were excluded. Outcomes were reported descriptively including therapeutic response, adverse effects (AEs), adherence (measured by proportion of days covered [PDC]), and discontinuation.ResultsThirty patients were included: 47% female, 93% White, median age 56 years. Most patients required dose escalations for inadequate response. The rate of AEs reported before and after transitioning to doses >48 mg/day was the same. Psychiatric changes were less commonly reported at doses >48 mg/day, but extrapyramidal symptoms were more common. The median total maximum chorea score in the Unified HD Rating Scale was 13 (IQR 9-19) and 13 (IQR 7-18) at baseline and follow-up, respectively. Median PDC was 0.99 (IQR 0.94-1.00); two patients discontinued therapy due to AEs.ConclusionsDeutetrabenazine >48 mg daily appears safe and well tolerated in patients with uncontrolled HD chorea, though no significant change in total maximal chorea score was found.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251323293"},"PeriodicalIF":2.1,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Through their eyes: A retrospective mixed-methods study on the experiences and support needs of children growing up with a parent with Huntington's disease.
IF 2.1
Journal of Huntington's disease Pub Date : 2025-02-01 Epub Date: 2024-12-19 DOI: 10.1177/18796397241304333
Maud Mj Daemen, Annelien A Duits, Lucienne B van der Meer, Ruben L Andriessen, Ruth B Veenhuizen, Renske Wassenberg, Tanja Peeters, Lia de Jager, Mayke Oosterloo
{"title":"Through their eyes: A retrospective mixed-methods study on the experiences and support needs of children growing up with a parent with Huntington's disease.","authors":"Maud Mj Daemen, Annelien A Duits, Lucienne B van der Meer, Ruben L Andriessen, Ruth B Veenhuizen, Renske Wassenberg, Tanja Peeters, Lia de Jager, Mayke Oosterloo","doi":"10.1177/18796397241304333","DOIUrl":"10.1177/18796397241304333","url":null,"abstract":"<p><p>BackgroundGrowing up with a parent with Huntington's disease (HD) profoundly impacts children. However, this impact and children's needs are often misunderstood, even by professional services. Even when resources are available, children often feel that their needs are unmet, raising concerns about the adequacy of available guidance and support.ObjectiveThis study aims to offer an in-depth understanding of the multifaceted impact of growing up with a parent with HD, examining the needs for professional guidance on emotional and social aspects, and identifying specific areas where support can be improved to better aid them.MethodsThis retrospective study utilized an exploratory sequential mixed methods design, combining qualitative focus groups (<i>n </i>= 13) and a quantitative survey (<i>n </i>= 23). Qualitative data were analyzed using an inductive thematic analysis with a descriptive phenomenological approach. Quantitative data were analyzed using descriptive statistics.ResultsThe impact of HD on children extends across various domains, affecting self-development, social interactions, and family dynamics. Support received at home varied, with limited access to professional help. Support needs primarily revolved around emotional support and access to comprehensive information. Key support providers, such as parents, peers, mentors, healthcare providers and coaches with expertise in HD, play crucial roles in addressing these needs.ConclusionsThe study underscores challenges faced by children in HD families. By centering our efforts on the emotional well-being of these children, offering tailored information, involving their social network, providing community-based support, and strengthening parental support systems, we can improve the support required by children in these families.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"93-102"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Economic burden of Huntington's disease: A systematic review.
IF 2.1
Journal of Huntington's disease Pub Date : 2025-02-01 Epub Date: 2025-02-10 DOI: 10.1177/18796397251319209
Pooja Gokhale, Lorenzo Villa Zapata
{"title":"Economic burden of Huntington's disease: A systematic review.","authors":"Pooja Gokhale, Lorenzo Villa Zapata","doi":"10.1177/18796397251319209","DOIUrl":"10.1177/18796397251319209","url":null,"abstract":"<p><p>BackgroundHuntington's disease (HD) is an autosomal dominant neurodegenerative disease, characterized by progressive motor, cognitive, and psychiatric symptoms. The disease poses a significant social and economic burden.ObjectiveThis systematic review aims to characterize the global economic burden by analyzing the direct, indirect, and total costs associated with HD.MethodsA comprehensive literature search was conducted across PubMed/MEDLINE, Web of Science, and Cochrane Library from inception to June 2024. The titles and abstracts were screened independently by two reviewers and full-text, English-language articles assessing direct, indirect, and/or total costs of HD were included. The costs were converted to annual costs in 2024 United States Dollars (USD).ResultsOut of the initial 608 de-duplicated articles, 19 full-text articles were included. The articles spanned 44 years, from 1980 to 2024. The studies covered a total of 15 countries. Annual costs in 2024 USD ranged significantly by region: Americas ($2542-$90,515), Europe ($40,000-$215,020), Asia ($1915-$7132), and Oceania ($3678-$8721). The highest costs were reported in Norway ($171,842) and the UK ($215,020), while Asian countries reported substantially lower costs (China: $6469; South Korea: $6305; Taiwan: $1915-$7132).ConclusionsThe global economic burden of HD varies substantially across regions, influenced by prevalence rates, healthcare systems, and reporting methodologies. Study limitations include heterogeneous cost reporting methods, potential underestimation in cost conversions, and lack of disease severity stratification. Standardizing cost-of-illness study methodologies and developing specific quality assessment tools would enhance cross-study comparability and improve resource allocation globally.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"30-42"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antidopaminergic medications in Huntington's disease.
IF 2.1
Journal of Huntington's disease Pub Date : 2025-02-01 Epub Date: 2025-01-12 DOI: 10.1177/18796397241304312
Andrew M Tan, Michal Geva, Y Paul Goldberg, Henk Schuring, Bernd-Jan Sanson, Anne Rosser, Lynn Raymond, Ralf Reilmann, Michael R Hayden, Karen Anderson
{"title":"Antidopaminergic medications in Huntington's disease.","authors":"Andrew M Tan, Michal Geva, Y Paul Goldberg, Henk Schuring, Bernd-Jan Sanson, Anne Rosser, Lynn Raymond, Ralf Reilmann, Michael R Hayden, Karen Anderson","doi":"10.1177/18796397241304312","DOIUrl":"10.1177/18796397241304312","url":null,"abstract":"<p><p>Huntington's disease (HD) is a progressive neurodegenerative disorder marked by motor, cognitive, and behavioral impairments. Antidopaminergic medications (ADMs), such as VMAT2 inhibitors and antipsychotics, are commonly used to manage HD motor disturbances and behavioral disorders. For patients and caregivers, ADMs are an important tool for managing symptoms that negatively affect daily life. However, the impact of ADM use in HD is not firmly understood due to a lack of robust, systematic studies that assessed their overall effect on HD disease. A mounting body of evidence suggests these medications may be associated with worse clinical measures of cognitive function and functional impairment. While regulatory guidelines highlight adverse effects like sedation, cognitive dysfunction, and extrapyramidal symptoms, it is unclear whether ADMs directly impact disease progression or if the side effects mimic or exacerbate measures of HD symptoms in clinical trials. Given ADM effects on the central nervous system and biological uncertainty within HD outcomes, clinical trial designs should recognize the impact of ADMs on key outcomes, as measured by acceptable scales including Total Functional Capacity, Stoop Word Reading, Symbol Digit Modality Test, and the composite Unified Huntington's Disease Rating Scale. The development of novel HD interventions requires consideration of concomitant ADM use that may influence measures of disease presentation. In this review, we highlight the role of ADMs in HD management, their symptomatic benefits and potential risks, especially with high dose associated side effects, interactions with CYP2D6 inhibitors, and the individualized need for careful dose monitoring for clinical care and trial design.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"16-29"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Upcoming meetings related to Huntington's disease.
IF 2.1
Journal of Huntington's disease Pub Date : 2025-02-01 Epub Date: 2025-02-27 DOI: 10.1177/18796397251323357
{"title":"Upcoming meetings related to Huntington's disease.","authors":"","doi":"10.1177/18796397251323357","DOIUrl":"10.1177/18796397251323357","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"109"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Frequency of depression in Huntington's disease: A systematic review and meta-analysis.
IF 2.1
Journal of Huntington's disease Pub Date : 2025-02-01 Epub Date: 2024-12-05 DOI: 10.1177/18796397241301774
Shayan Abdollah Zadegan, Frank Ramirez, Jung Woo Park, Natalia Pessoa Rocha, Erin Furr Stimming, Antonio L Teixeira
{"title":"Frequency of depression in Huntington's disease: A systematic review and meta-analysis.","authors":"Shayan Abdollah Zadegan, Frank Ramirez, Jung Woo Park, Natalia Pessoa Rocha, Erin Furr Stimming, Antonio L Teixeira","doi":"10.1177/18796397241301774","DOIUrl":"10.1177/18796397241301774","url":null,"abstract":"<p><p>BackgroundHuntington's disease (HD) is a hereditary neurodegenerative disease characterized by a combination of motor, cognitive, and mental health issues, with depression being the most common. Despite its importance, the relationship between depression and disease progression is still debatable.ObjectiveThe primary objective of this study was to examine the frequency of depression across different disease stages in individuals with HD. We also explored the associations between depression and other HD-related factors.MethodsThis systematic review comprehensively searched MEDLINE, APA PsycINFO, and Embase databases for studies on depression in individuals with HD. Pooled depression frequencies were calculated for premanifest and manifest HD. Depression was analyzed based on HD functional stages and diagnostic tools, alongside reviewing its association with various HD factors.ResultsWe assessed 6523 records and included 104 studies. Our meta-analyses revealed that the overall frequency of depression was higher in manifest HD compared to premanifest HD (0.38 vs. 0.23). However, the progression of depression did not follow a consistent pattern, with peaks occurring in earlier rather than later stages. Additionally, the frequency of depression was lower in studies using diagnostic criteria compared to those using clinical scales (0.25 vs. 0.42).ConclusionsOur findings showed that the rate of depression is high in HD and varies depending on the disease stage and the criteria used. This emphasizes the necessity for tailored and unified diagnostic criteria for depression in HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"43-58"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Absence of hippocampal pathology persists in the Q175DN mouse model of Huntington's disease despite elevated HTT aggregation.
IF 2.1
Journal of Huntington's disease Pub Date : 2025-02-01 Epub Date: 2025-02-03 DOI: 10.1177/18796397251316762
Melissa A Solem, Ross G Pelzel, Nicholas B Rozema, Taylor G Brown, Emma Reid, Rachel H Mansky, Rocio Gomez-Pastor
{"title":"Absence of hippocampal pathology persists in the Q175DN mouse model of Huntington's disease despite elevated HTT aggregation.","authors":"Melissa A Solem, Ross G Pelzel, Nicholas B Rozema, Taylor G Brown, Emma Reid, Rachel H Mansky, Rocio Gomez-Pastor","doi":"10.1177/18796397251316762","DOIUrl":"10.1177/18796397251316762","url":null,"abstract":"<p><p>BackgroundHuntington's disease (HD) is a neurodegenerative disorder causing motor, cognitive, and psychiatric impairments, with the striatum being the most affected brain region. However, the role of other regions, such as the hippocampus, in HD remains less understood.ObjectiveHere, we study the comparative impact of enhanced mHTT aggregation and neuropathology in the striatum and hippocampus of two HD mouse models.MethodsWe utilized the zQ175 as a control HD mouse model and the Q175DN mice lacking the PGK-Neomycin cassette generated in house. We performed a comparative characterization of the neuropathology between zQ175 and Q175DN mice in the striatum and the hippocampus by assessing HTT aggregation, neuronal and glial pathology, chaperone expression, and synaptic density.ResultsWe showed that Q175DN mice presented enhanced mHTT aggregation in both striatum and hippocampus compared to zQ175. Striatal neurons showed a greater susceptibility to enhanced accumulation of mHTT in Q175DN. On the contrary, no signs of hippocampal pathology were found in zQ175 and absence of hippocampal pathology persisted in Q175DN mice despite higher levels of mHTT. In addition, Q175DN hippocampus presented increased synaptic density, decreased Iba1<sup>+</sup> microglia density and enhanced HSF1 levels in specific subregions of the hippocampus compared to zQ175.ConclusionsQ175DN mice are a valuable tool to understand the fundamental susceptibility differences to mHTT toxicity between striatal neurons and other neuronal subtypes. Furthermore, our findings also suggest that cognitive deficits observed in HD animals might arise from either striatum dysfunction or other regions involved in cognitive processes but not from hippocampal degeneration.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"59-84"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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