Neurodegenerative Diseases最新文献

{"title":"Clinical Manifestations Associated with the Domain-Containing Protein 2 Gene Mutation in an Iranian Family with Spastic Paraplegia 54.","authors":"Abolfazl Yari,&nbsp;Shokoofeh Etesam,&nbsp;Shannaz Zarifi,&nbsp;Sepideh Parvizpour,&nbsp;Ebrahim Miri-Moghaddam","doi":"10.1159/000530375","DOIUrl":"10.1159/000530375","url":null,"abstract":"<p><strong>Introduction: </strong>Spastic paraplegia type 54 (SPG54) is an autosomal recessive disorder caused by bi-allelic mutations in the DDHD-domain-containing protein 2 (DDHD2) gene. Worldwide, over 24 SPG54 families and 24 pathogenic variants have been reported. Our study aimed to describe the clinical and molecular findings of a pediatric patient from a consanguineous Iranian family with significant motor development delay, walking problems, paraplegia, and optic atrophy.</p><p><strong>Methods: </strong>The patient was a 7-year-old boy with severe neurodevelopmental and psychomotor problems. Neurological examinations, laboratory tests, electroencephalography, computed tomography scan, and brain magnetic resonance scan (MRI) were carried out for clinical evaluation. Whole-exome sequencing and in silico analysis were undertaken to identify the genetic cause of the disorder.</p><p><strong>Results: </strong>The neurological examination showed developmental delay, spasticity in the lower extremities, ataxia, foot contractures, and deep tendon reflexes in the extremities. The computed tomography scan was normal, but MRI revealed corpus callosum thinning with atrophic changes in the white matter. The genetic study reported a homozygous variant (c.856 C&gt;T, p.Gln286Ter) in the DDHD2 gene. The homozygous state was confirmed by direct sequencing in the proband and his 5-year-old brother. This variant was not reported as a pathogenic variant in the literature or genetic databases and was predicted to affect the function of the DDHD2 protein.</p><p><strong>Conclusion: </strong>The clinical symptoms in our cases were similar to the previously reported phenotype of SPG54. Our results deepen the molecular and clinical spectrum of SPG54 to facilitate future diagnoses.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"139-150"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9553128","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":"Early Autonomic Symptoms Predict Functional Decline in Parkinson's Disease Independent of Dopaminergic Therapy.","authors":"Cameron Miller-Patterson,&nbsp;Jesse Y Hsu,&nbsp;Lana M Chahine","doi":"10.1159/000525664","DOIUrl":"https://doi.org/10.1159/000525664","url":null,"abstract":"<p><strong>Introduction: </strong>Parkinson's disease (PD) has variable progression; identifying determinants of functional decline in PD is needed for accurate prognostication. Autonomic symptoms can result from dopaminergic therapy but may also independently predict functional decline.</p><p><strong>Methods: </strong>The sample included individuals with newly diagnosed PD in Parkinson's Progression Markers Initiative. Autonomic symptoms were measured with the Scales-for-Outcomes-in-Parkinson's-Disease-Autonomic (SCOPA-AUT). Presence/absence of autonomic symptoms for SCOPA-AUT total scale and seven subscales was defined, and baseline demographic/clinical data were compared between groups with and without autonomic symptoms. Time-to-functional-dependence, or Schwab-and-England Activities-of-Daily-Living (SE-ADL) ≤70, was compared between groups using hazard models, adjusting for covariates including time-varying levodopa-equivalent daily dosage. If a subscale was associated with a significant subhazard ratio (SHR), hazard models for items in that subscale were generated and gender was evaluated as an effect modifier.</p><p><strong>Results: </strong>399 participants were included. Over a median of 72 months (range 6-84), 91 (22.81%) reached SE-ADL ≤70. SCOPA-AUT total/gastrointestinal/urinary/pupillomotor scales were associated with SE-ADL ≤70; respective multivariable SHRs (95% CI, p value) were 1.98 (1.06-3.70, 0.03), 1.71 (1.04-2.81, 0.03), 1.94 (1.25-3.01, <0.01), 2.56 (1.24-5.31, 0.01). Individual items in the gastrointestinal and urinary scales drove associations. Urinary scale associations were seen in males only.</p><p><strong>Conclusions: </strong>Symptoms of gastrointestinal, urinary, pupillomotor dysfunction are associated with functional decline risk in PD, independent of dopaminergic therapy. Detailed assessments of autonomic symptomatology should be utilized in studies attempting to refine predictive models of PD progression.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"22 1","pages":"15-23"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9671814/pdf/nihms-1822986.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9750579","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 Immunomodulatory Potential Role of Mesenchymal Stem Cells in Diseases of the Central Nervous System.","authors":"Rodrigo de Andrade Rufino,&nbsp;Laís da Silva Pereira-Rufino,&nbsp;Thays Cristina Silva Vissoto,&nbsp;Irina Kerkis,&nbsp;Adriana da Costa Neves,&nbsp;Marcelo Cavenaghi Pereira da Silva","doi":"10.1159/000528036","DOIUrl":"https://doi.org/10.1159/000528036","url":null,"abstract":"<p><strong>Introduction: </strong>Several studies indicate the role of mesenchymal stem cells (MSCs) as an important tool in regenerative medicine associated with injuries that affect the central nervous system (CNS). The MSCs have the capacity to differentiate into cells of the embryonic tissue, such as the mesoderm. So, these cells can be found in a variety of tissues. Also, the MSCs can release immunomodulatory and neurotrophic factors performance as inflammation mediators operating in injured tissue regeneration. Furthermore, they can differentiate into neural-like cells in vitro. Thereby, because of the high immunomodulatory role of MSCs, this review sought to describe the main immunomodulatory mechanisms performed by MSCs in CNS recovery after tissue injury or neurodegenerative diseases.</p><p><strong>Methods: </strong>PubMed and ScienceDirect were searched between January 2011 to March 2021, and 43 articles met the criteria of the review.</p><p><strong>Results: </strong>This systematic review indicates that MSCs were used in vivo experimental multiple sclerosis, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, ischemic stroke, and traumatic brain injury. The treatment MSCs were usually from human origin, derived from bone marrow, and administered intravenously.</p><p><strong>Conclusion: </strong>It was shown that MSCs, independent from origin or administration pathway, can reduce inflammation and help in the recovery and preservation of injured neural tissue. Thus, the use of MSCs represents a potential therapeutic option in the treatment of neurological disorders mediated by inflammatory processes.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"22 2","pages":"68-82"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10626854","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":"Natural Age-Related Slow-Wave Sleep Alterations Onset Prematurely in the Tg2576 Mouse Model of Alzheimer's Disease.","authors":"Sedef Kollarik,&nbsp;Inês Dias,&nbsp;Carlos G Moreira,&nbsp;Dorita Bimbiryte,&nbsp;Djordje Miladinovic,&nbsp;Joachim M Buhmann,&nbsp;Christian R Baumann,&nbsp;Daniela Noain","doi":"10.1159/000527786","DOIUrl":"https://doi.org/10.1159/000527786","url":null,"abstract":"<p><strong>Introduction: </strong>Sleep insufficiency or decreased quality have been associated with Alzheimer's disease (AD) already in its preclinical stages. Whether such traits are also present in rodent models of the disease has been poorly addressed, somewhat disabling the preclinical exploration of sleep-based therapeutic interventions for AD.</p><p><strong>Methods: </strong>We investigated age-dependent sleep-wake phenotype of a widely used mouse model of AD, the Tg2576 line. We implanted electroencephalography/electromyography headpieces into 6-month-old (plaque-free, n = 10) and 11-month-old (moderate plaque-burdened, n = 10) Tg2576 mice and age-matched wild-type (WT, 6 months old n = 10, 11 months old n = 10) mice and recorded vigilance states for 24 h.</p><p><strong>Results: </strong>Tg2576 mice exhibited significantly increased wakefulness and decreased non-rapid eye movement sleep over a 24-h period compared to WT mice at 6 but not at 11 months of age. Concomitantly, power in the delta frequency was decreased in 6-month old Tg2576 mice in comparison to age-matched WT controls, rendering a reduced slow-wave energy phenotype in the young mutants. Lack of genotype-related differences over 24 h in the overall sleep-wake phenotype at 11 months of age appears to be the result of changes in sleep-wake characteristics accompanying the healthy aging of WT mice.</p><p><strong>Conclusion: </strong>Therefore, our results indicate that at the plaque-free disease stage, diminished sleep quality is present in Tg2576 mice which resembles aged healthy controls, suggesting an early-onset of sleep-wake deterioration in murine AD. Whether such disturbances in the natural patterns of sleep could in turn worsen disease progression warrants further exploration.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"22 2","pages":"55-67"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9279886","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":"Association between Gut Microbiota with Mild Cognitive Impairment and Alzheimer's Disease in a Thai Population.","authors":"Pagakrong Wanapaisan,&nbsp;Mallika Chuansangeam,&nbsp;Saifon Nopnipa,&nbsp;Rubwad Mathuranyanon,&nbsp;Nutthawan Nonthabenjawan,&nbsp;Chanon Ngamsombat,&nbsp;Tanyaluck Thientunyakit,&nbsp;Weerasak Muangpaisan","doi":"10.1159/000526947","DOIUrl":"https://doi.org/10.1159/000526947","url":null,"abstract":"<p><strong>Background: </strong>Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are common in older adults. Much recent work has implicated the connection between the gut and the brain via bidirectional communication of the gastrointestinal tract and the central nervous system through biochemical signaling. Altered gut microbiota composition has shown controversial results based on geographic location, age, diet, physical activity, psychological status, underlying diseases, medication, and drug use.</p><p><strong>Objectives: </strong>This study aimed to investigate the relationships of gut microbiota with MCI and AD.</p><p><strong>Methods: </strong>16S metagenome profiles from stool collection of participant groups (normal; n = 20, MCI; n = 12, AD; n = 20) were analyzed. The diagnosis of cognitive conditions was made by standard criteria consisting of clinical interviews, physical examinations, cognitive assessments, laboratory examinations, and neuroimaging by both structural neuroimaging and amyloid positron emission tomography scans. Correlations between medical factors with food frequency and the fecal microbiome were elucidated.</p><p><strong>Results: </strong>A significant difference at the operational taxonomic unit level was observed. The significantly higher abundance of bacteria in nondementia patients belonged to the Clostridiales order, including Clostridium sensu stricto 1 (p < 0.0001), Fusicatenibacter (p = 0.0007), Lachnospiraceae (p = 0.001), Agathobacter (p = 0.021), and Fecalibacterium (p < 0.0001). In contrast, Escherichia-Shigella (p = 0.0002), Bacteroides (p = 0.0014), Holdemanella (p < 0.0001), Romboutsia (p = 0.001), and Megamonas (p = 0.047) were the dominant genera in the AD group. Left and right hippocampus and right amygdala volumes were significantly decreased in the AD group (p < 0.001) and significantly correlated with the groups of bacteria that were significantly different between groups.</p><p><strong>Conclusion: </strong>There was a relationship between the composition of the gut microbiome and neurodegenerative disorders, including MCI and AD. Reduction of Clostridiaceae and increases in Enterobacteriaceae and Bacteroides were associated with persons with MCI and AD, consistent with previous studies. The altered gut microbiome could be potentially targeted for the early diagnosis of dementia and the reduction of AD risk.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"22 2","pages":"43-54"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10564446","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":"CSF Aβ40 Levels Do Not Correlate with the Clinical Manifestations of Alzheimer's Disease.","authors":"Jesús Garcia Castro,&nbsp;Helena Méndez Del Sol,&nbsp;Olaia Rodríguez Fraga,&nbsp;María Hernández Barral,&nbsp;Soledad Serrano López,&nbsp;Ana Frank García,&nbsp;Ángel Martín Montes","doi":"10.1159/000530907","DOIUrl":"10.1159/000530907","url":null,"abstract":"<p><strong>Introduction: </strong>Cerebrospinal fluid (CSF) biomarker quantification provides physicians with a reliable diagnosis of Alzheimer's disease (AD). However, the relationship between their concentration and disease course has not been clearly elucidated. This work aimed to investigate the clinical and prognostic significance of Aβ40 CSF levels.</p><p><strong>Methods: </strong>A retrospective cohort of 76 patients diagnosed with AD using a decreased Aβ42/Aβ40 ratio was subclassified into hyposecretors (Aβ40 &lt;7,755 pg/mL), normosecretors (Aβ40 7,755-16,715 pg/mL), and hypersecretors (Aβ40 &gt;16,715 pg/mL). Potential differences in AD phenotype, Montreal Cognitive Assessment (MoCA) scores, and Global Deterioration Scale (GDS) stages were assessed. Correlation tests for biomarker concentrations were also performed.</p><p><strong>Results: </strong>Participants were classified as hyposecretors (n = 22, median Aβ40 5,870.500 pg/mL, interquartile range [IQR] 1,431), normosecretors (n = 47, median Aβ40 10,817 pg/mL, IQR 3,622), and hypersecretors (n = 7, 19,767 pg/mL, IQR 3,088). The distribution of positive phosphorylated Tau (p-Tau) varied significantly between subgroups and was more common in the normo- and hypersecretor categories (p = 0.003). Aβ40 and p-Tau concentrations correlated positively (ρ = 0.605, p &lt; 0.001). No significant differences were found among subgroups regarding age, initial MoCA score, initial GDS stage, progression to the dementia stage, or changes in the MoCA score.</p><p><strong>Conclusion: </strong>In this study, we found no significant differences in clinical symptoms or disease progression in AD patients according to their CSF Aβ40 concentration. Aβ40 was positively correlated with p-Tau and total Tau concentrations, supporting their potential interaction in AD pathophysiology.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"151-158"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9876682","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 Two-Way Route between Delirium Disorder and Dementia: Insights from COVID-19.","authors":"Giulia Bommarito,&nbsp;Valentina Garibotto,&nbsp;Giovanni B Frisoni,&nbsp;Frédéric Assal,&nbsp;Patrice H Lalive,&nbsp;Gilles Allali","doi":"10.1159/000530566","DOIUrl":"10.1159/000530566","url":null,"abstract":"<p><strong>Background: </strong>Delirium disorder is a frequent neurological complication of SARS-CoV-2 infection and associated with increased disease severity and mortality. Cognitive impairment is a major risk factor for developing delirium disorder during COVID-19, which, in turn, increases the risk of subsequent neurological complications and cognitive decline.</p><p><strong>Summary: </strong>The bidirectional connection between delirium disorder and dementia likely resides at multiple levels, and its pathophysiological mechanisms during COVID-19 include endothelial damage, blood-brain barrier dysfunction, and local inflammation, with activation of microglia and astrocytes. Here, we describe the putative pathogenic pathways underlying delirium disorder during COVID-19 and highlight how they cross with the ones leading to neurodegenerative dementia.</p><p><strong>Key messages: </strong>The analysis of the two-sided link can offer useful insights for confronting with long-term neurological consequences of COVID-19 and framing future prevention and early treatment strategies.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"91-103"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9347424","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":"Front & Back Matter","authors":"P. Unschuld, R. Nitsch, S. DeKosky","doi":"10.1159/000521471","DOIUrl":"https://doi.org/10.1159/000521471","url":null,"abstract":"","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"21 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42638315","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":"Acknowledgement to Reviewers","authors":"","doi":"10.1159/000519810","DOIUrl":"https://doi.org/10.1159/000519810","url":null,"abstract":"© 2021 S. Karger AG, Basel karger@karger.com www.karger.com/ndd Karger Publishers and the editors of Neurodegenerative Diseases would like to thank the reviewers for the ongoing support in reviewing manuscripts for our Journal in 2021. This year we have chosen not to disclose the names of our reviewers to preserve the principle of anonymity inherent to the single-blind peer-review we follow. Even so, this should not be in our way to sincerely thank all contributing reviewers who have volunteered their time, effort, and expertise in benefit of the quality of the manuscripts we received and published in 2021. Individual reviewers can still claim their personal “Certificate of Review” via the Journal’s manuscript submission system.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 1","pages":"217 - 217"},"PeriodicalIF":3.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48224093","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":"Front & Back Matter","authors":"N. Zimmerman","doi":"10.1159/000517132","DOIUrl":"https://doi.org/10.1159/000517132","url":null,"abstract":"","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"1 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45357330","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}