Neurodegenerative Diseases最新文献

{"title":"Erratum.","authors":"","doi":"10.1159/000548755","DOIUrl":"10.1159/000548755","url":null,"abstract":"<p><p><body><sec id=\"s1\"><title /><p>In the article \"Active Immunization Targeting Amyloid β for the Treatment of Alzheimer's Disease\" [Neurodegener Dis. 2025; <ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"doi\" xlink:href=\"https://doi.org/10.1159/000546287\">https://doi.org/10.1159/000546287</ext-link>] by Triplett et al., the wrong copyright license was displayed. It has been corrected to a CC-BY 4.0 license. The section title was also corrected to Review Article.</p><p>The original online article has been updated to reflect this.</p></sec></body>.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"228"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145409776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Genetic Architecture of Parkinson's Disease in Morocco: Highlighting a Predominance of Mendelian Genes.","authors":"Ahmed Bouhouche, Houyam Tibar, Wafa Regragui","doi":"10.1159/000546424","DOIUrl":"10.1159/000546424","url":null,"abstract":"<p><p><p>Background: Parkinson's disease (PD), although widely heterogeneous and manifesting with numerous motor and non-motor symptoms, presents clinically as a single entity worldwide. Its genetic causes are also heterogeneous and include highly penetrant variants in a single gene representing rare monogenic forms, and rare or common variants conferring a relative disease risk representing more frequent multigenic forms. Most of these variants have been discovered in patients of European ancestry. Since the genetic basis of PD can vary significantly between populations due to differences in allele frequencies, little is known about the genetics of PD in other populations, particularly from Africa. Morocco, located in a region of North Africa, constitutes a subcontinent known for a weak external genetic influence and for a local genetic continuity for millennia, which makes it a region of interest to study the genetic causes of PD. Summary: This review aimed to summarize published research data on the genetic profile of PD patients from the Moroccan population to describe its genetic architecture. Unlike in Western countries, PD in Morocco is predominantly a Mendelian disease reaching up to 50%, due to the high prevalence of the LRRK2 G2019S dominant variant and to relatively less frequent PRKN and PINK1 recessive variants due to the high rate of consanguinity. Additionally, rare high-risk variants in LRRK2, VPS13C, MAPT, and POLG, in oligo- or polygenic ways, may contribute to increasing the genetic risk of the disease. Key Messages: We, therefore, show that the genetic architecture of PD in Morocco, a country in the subcontinent of North Africa, was different from that of sub-Saharan Africa and the rest of the world. This will help improve diagnostic accuracy, subdivide the clinical variability of the disease into groups of common genetic and biological causes for a better therapeutic management strategy, and test molecules from ongoing clinical trials. </p>.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"126-133"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Active Immunization Targeting Amyloid β for the Treatment of Alzheimer's Disease.","authors":"Olivia Triplett, Nicole Varda, Boris Decourt, Rodrigo Vasconcellos, Marwan N Sabbagh","doi":"10.1159/000546287","DOIUrl":"10.1159/000546287","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is the most prevalent neurodegenerative condition worldwide. It is characterized by the formation of amyloid beta (Aβ) plaques in the brain and by the accumulation of neurofibrillary tangles; the disease is marked by cognitive decline and memory impairment over time. Although cholinesterase inhibitors and <sc>N</sc>-methyl-<sc>D</sc>-aspartate receptor antagonists have been used to relieve symptoms, immunotherapies to treat the disease itself by targeting removal of amyloid are now beginning to be applied clinically. However, methods that allow the control of AD symptoms and that would require only a few clinical follow-ups are often preferred by patients. Thus, active immunization, or vaccination, against Aβ and tau is still being explored as a possible therapeutic intervention.</p><p><strong>Summary: </strong>This review aims to describe ongoing and discontinued immunization trials to treat AD. We conducted a comprehensive review of the literature to analyze the current status of vaccinations for AD. We examined and summarized the studies and clinical trials that explored the efficacy, safety, and challenges associated with this therapeutic approach.</p><p><strong>Key messages: </strong>This review highlights the potential for vaccination development to treat AD, including its efficacy, associated complications, and limitations. Much progress has been made over the past 2 decades, but challenges remain. Immunization is a promising avenue for treating or preventing symptomatic AD, offering potential benefits beyond symptomatic relief. Because challenges such as immunogenicity and safety profiles need to be addressed, further research and development are necessary to meet the growing demand for patient-acceptable, effective AD treatments.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"202-217"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Neurofilament Light-Chain Levels in Essential Tremor: A Replication Study.","authors":"Elan D Louis, Vibhash D Sharma, Ihab Hajjar, Nora Hernandez","doi":"10.1159/000542922","DOIUrl":"10.1159/000542922","url":null,"abstract":"<p><strong>Introduction: </strong>Essential tremor (ET) is a highly prevalent neurological disease. At present, there are no clinical biomarkers. Neurofilament light (NfL) has been studied as a measure of neuronal damage in a considerable number of neurological disorders. There have been three studies of ET, and results are inconsistent.</p><p><strong>Methods: </strong>Forty ET cases were enrolled in a research study between February and November 2023 and compared to two control groups from study 1 (n = 41) and study 2 (n = 185). Total tremor score was a measure of the severity of action tremor. Blood samples were analyzed for serum NfL level on the Simoa® platform using an NF-Light™ kit as a marker of axonal injury.</p><p><strong>Results: </strong>Serum log NfL levels were higher in ET cases than controls in study 1 (p < 0.001) and study 2 (p < 0.001). In a multivariate linear regression model, ET cases (p = 0.03) and individuals of older age (p < 0.001) had higher serum log NfL levels than controls (combined in studies 1 and 2). There was no association in ET cases between serum log NfL level and total tremor score (Pearson's r = 0.08, p = 0.63).</p><p><strong>Conclusion: </strong>This new study further validates the elevation in serum NfL levels in ET, now representing the third study to do so. In combination, the converging data suggest that there is an overall increase in serum NfL levels in ET. The demonstration of elevated serum levels of NfL in ET adds an additional piece of evidence that there is neuronal damage in ET.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"141-147"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12731585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Biomarkers for Alzheimer's Disease: Unlocking the Diagnostic Potential in Low- and Middle-Income Countries, Focusing on Africa.","authors":"Luc Nwamekang Belinga, Jeanne Espourteille, Yembe Wepnyu Njamnshi, Ariole Zafack Zeukang, Olivier Rouaud, Alfred Kongnyu Njamnshi, Gilles Allali, Kevin Richetin","doi":"10.1159/000538623","DOIUrl":"10.1159/000538623","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is emerging as a significant public health challenge in Africa, with predictions indicating a tripling in incidence by 2050. The diagnosis of AD on the African continent is notably difficult, leading to late detection that severely limits treatment options and significantly impacts the quality of life for patients and their families.</p><p><strong>Summary: </strong>This review focuses on the potential of high-sensitivity specific blood biomarkers as promising tools for improving AD diagnosis and management globally, particularly in Africa. These advances are particularly pertinent in the continent, where access to medical and technical resources is often limited.</p><p><strong>Key messages: </strong>Identifying precise, sensitive, and specific blood biomarkers could contribute to the biological characterization and management of AD in Africa. Such advances promise to improve patient care and pave the way for new regional opportunities in pharmaceutical research and drug trials on the continent for AD.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"26-40"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"20th Anniversary of Neurodegenerative Diseases: A Parallel (R)Evolution between the 20th and the 21st Century?","authors":"Gilles Allali","doi":"10.1159/000539440","DOIUrl":"10.1159/000539440","url":null,"abstract":"","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"2-5"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Drug Interactions on the Results of DAT-SPECT Imaging in a Specialty Movement Disorders Practice: A Retrospective Analysis of Outcomes.","authors":"Isabelle Heewon Kang, Danny Bega","doi":"10.1159/000540105","DOIUrl":"10.1159/000540105","url":null,"abstract":"<p><strong>Introduction: </strong>DAT-SPECT imaging is approved as a diagnostic tool for the evaluation of suspected Parkinsonian syndromes, but the FDA-approved package insert lists 16 potential drugs that may interfere with the image obtained. The clinical impact of these drugs on imaging results has not been established. This study aimed to determine the accuracy of DAT-SPECT imaging in assessing presynaptic dopaminergic denervation in the setting of these drugs.</p><p><strong>Methods: </strong>This is a retrospective chart review of patients at a single center who underwent DAT-SPECT imaging while taking \"contraindicated\" drugs between December 2012 and December 2022.</p><p><strong>Results: </strong>A total of 1,224 charts were screened, and 153 (12.5%) charts met the inclusion criteria. Bupropion (32%, n = 49) and sertraline (26%, n = 40) were the most common contraindicated drugs. The false-positive rate was 9.2%.</p><p><strong>Conclusion: </strong>This retrospective analysis supports the concern that certain drugs may interfere with DAT-SPECT imaging results, leading to potential false positives. This has implications for how clinicians interpret DAT-SPECT imaging in patients taking these medications and whether they should advise patients to stop these medications before a scan is performed.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"91-96"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole Exome Sequencing Indicating GGCCTG Hexanucleotide Repeat in Patients with Spinocerebellar Ataxia Type 36.","authors":"Ran Chen, Chao Zhou, Yun Peng, Pengcheng Huang, Yanyan Yu, Min Zhu, Meihong Zhou, Daojun Hong, Dandan Tan","doi":"10.1159/000540006","DOIUrl":"10.1159/000540006","url":null,"abstract":"<p><strong>Introduction: </strong>Spinocerebellar ataxia type 36 (SCA36) is caused by large GGCCTG repeat expansion in the NOP56 gene. The genetic diagnosis based on Southern blot is expensive and time-consuming. This study aimed to evaluate the reliability and effectiveness of whole exome sequencing (WES) for routine genetic diagnosis of suspected SCA36 patients.</p><p><strong>Methods: </strong>Pathogenic repeat expansions for SCAs including SCA36 were first analyzed based on WES data using ExpansionHunter in five probands from SCA families, then the results were confirmed by triplet repeat primed polymerase chain reaction (TP-PCR) and Southern blot.</p><p><strong>Results: </strong>GGCCTG repeat expansion in NOP56 was indicated in all five probands by WES, then it was found in 11 SCA patients and three asymptomatic individuals by TP-PCR. The sizes of GGCCTG repeat expansions were confirmed to be 1,390-1,556 by Southern blot. The mean age at onset of the patients was 51.0 ± 9.3 (ranging from 41 to 71), and they presented slowly progressive cerebellar ataxia, atrophy and fasciculation in tongue or limb muscles.</p><p><strong>Conclusion: </strong>The patients were clinically and genetically diagnosed as SCA36. This study proposed that WES could be a rapid, reliable, and cost-effective routine test for the preliminarily detection of SCA36 and other ataxia diseases.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"71-79"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Classification of Mild Cognitive Impairment and Alzheimer's Disease Using Manual Motor Measures.","authors":"Vincent Koppelmans, Marit F L Ruitenberg, Sydney Y Schaefer, Jace B King, Jasmine M Jacobo, Benjamin P Silvester, Amanda F Mejia, Jos van der Geest, John M Hoffman, Tolga Tasdizen, Kevin Duff","doi":"10.1159/000539800","DOIUrl":"10.1159/000539800","url":null,"abstract":"<p><strong>Introduction: </strong>Manual motor problems have been reported in mild cognitive impairment (MCI) and Alzheimer's disease (AD), but the specific aspects that are affected, their neuropathology, and potential value for classification modeling is unknown. The current study examined if multiple measures of motor strength, dexterity, and speed are affected in MCI and AD, related to AD biomarkers, and are able to classify MCI or AD.</p><p><strong>Methods: </strong>Fifty-three cognitively normal (CN), 33 amnestic MCI, and 28 AD subjects completed five manual motor measures: grip force, Trail Making Test A, spiral tracing, finger tapping, and a simulated feeding task. Analyses included (1) group differences in manual performance; (2) associations between manual function and AD biomarkers (PET amyloid β, hippocampal volume, and APOE ε4 alleles); and (3) group classification accuracy of manual motor function using machine learning.</p><p><strong>Results: </strong>Amnestic MCI and AD subjects exhibited slower psychomotor speed and AD subjects had weaker dominant hand grip strength than CN subjects. Performance on these measures was related to amyloid β deposition (both) and hippocampal volume (psychomotor speed only). Support vector classification well-discriminated control and AD subjects (area under the curve of 0.73 and 0.77, respectively) but poorly discriminated MCI from controls or AD.</p><p><strong>Conclusion: </strong>Grip strength and spiral tracing appear preserved, while psychomotor speed is affected in amnestic MCI and AD. The association of motor performance with amyloid β deposition and atrophy could indicate that this is due to amyloid deposition in and atrophy of motor brain regions, which generally occurs later in the disease process. The promising discriminatory abilities of manual motor measures for AD emphasize their value alongside other cognitive and motor assessment outcomes in classification and prediction models, as well as potential enrichment of outcome variables in AD clinical trials.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"54-70"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Taxonomy of Subjective Cognitive Decline: Proposal and First Clinical Evidence from the Geneva Memory Clinic Cohort.","authors":"Federica Ribaldi, Rafael Palomo, Daniele Altomare, Max Scheffler, Frederic Assal, Nicholas J Ashton, Henrik Zetterberg, Kaj Blennow, Marc Abramowicz, Valentina Garibotto, Christian Chicherio, Giovanni B Frisoni","doi":"10.1159/000539053","DOIUrl":"10.1159/000539053","url":null,"abstract":"<p><strong>Introduction: </strong>Subjective cognitive decline (SCD) is characterized by subjective cognitive concerns without objective cognitive impairment and is considered a risk factor for cognitive decline and dementia. However, most SCD patients will not develop neurodegenerative disorders, yet they may suffer from minor psychiatric, neurological, or somatic comorbidities. The aim of the present study was to provide a taxonomy of the heterogeneous SCD entity and to conduct a preliminary validation using data from a memory clinic sample.</p><p><strong>Methods: </strong>Participants were fifty-five SCD individuals consecutively recruited at the Geneva Memory Center. Based on clinical reports, they were classified into three clinically pre-defined subgroups: (i) those with psychological or psychiatric comorbidities (Psy), (ii) those with somatic comorbidities (SomCom), (iii) and those with no apparent cause (NAC). Baseline demographics, clinical, cognitive, and biomarker differences among the SCD subgroups were assessed. Longitudinal cognitive changes (average 3 years follow-up) were modeled using a linear mixed model.</p><p><strong>Results: </strong>Out of the 55 SCD cases, 16 were SomCom, 18 Psy, and 21 NAC. 47% were female, mean age was 71 years. We observed higher frequency of APOE ε4 carriers in NAC (53%) compared to SomCom (14%) and Psy (0%, p = 0.023) and lower level of plasma Aβ42 in NAC (6.8 ± 1.0) compared to SomCom (8.4 ± 1.1; p = 0.031). SomCom subjects were older (74 years) than Psy (67 years, p = 0.011), and had greater medial temporal lobe atrophy (1.0 ± 1.0) than Psy (0.2 ± 0.6) and NAC (0.4 ± 0.5, p = 0.005). SomCom has worse episodic memory performances (14.5 ± 3.5) than Psy (15.8 ± 0.4) and NAC (15.8 ± 0.7, p = 0.032). We observed a slightly steeper, yet not statistically significant, cognitive decline in NAC (β = -0.48) compared to Psy (β = -0.28) and SomCom (β = -0.24).</p><p><strong>Conclusions: </strong>NAC features a higher proportion of APOE ε4 carriers, lower plasma Aβ42 and a trend towards steeper cognitive decline than SomCom and Psy. Taken together, these findings suggest that NACs are at higher risk of cognitive decline due to AD. The proposed clinical taxonomy might be implemented in clinical practice to identify SCD at higher risk. However, such taxonomy should be tested on an independent cohort with a larger sample size.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"16-25"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}