Neurodegenerative Diseases最新文献

{"title":"Alzheimer's disease, β-amyloid peptides and ubiquitin-proteasome system: nutritherapeutic insights.","authors":"Philippe Yves Rémy Simon, Renaud David","doi":"10.1159/000545170","DOIUrl":"https://doi.org/10.1159/000545170","url":null,"abstract":"<p><strong>Background: </strong>The Alzheimer's disease - an age-related neurodegenerative disorder leading to a progressive cognitive impairment - is characterized by an intracerebral accumulation of soluble β-amyloid (Aβ) oligomers, followed by the appearance of abnormally ubiquitinylated neurofibrillary tangles - a process associated with a chronic inflammation. The systematic presence of ubiquitinylated inclusions reflects a decrease in the proteasome activity due to (and contributing to) the presence of Aβ oligomers - a central dysfunction in the etiology of the disease.</p><p><strong>Summary: </strong>The involvement of the ubiquitin-proteasome system opens new therapeutic perspectives for both prevention and treatment. In particular, the potential for synergistic strategies combining diet-derived proteasome activators, immunoproteasome inhibitors and modulators of β-amyloid peptide aggregation to prevent delay or even reverse the disease progression over time is currently arousing growing interest.</p><p><strong>Key messages: </strong>In that perspective, and in the light of the recent advances in the understanding of the key molecular and cellular mechanisms underlying the Alzheimer's disease pathogenesis, the present review highlights the mechanisms of action and the preventive and therapeutic potential of some diet-derived bioactive compounds and other natural substances of interest. This article is a translated, updated and expanded version of an article originally published in French in Médecine/Sciences, August/September 2023 (https://doi.org/10.1051/medsci/2023094).</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"1-23"},"PeriodicalIF":1.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710710","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":"Sex differences in progression of neurodegeneration: the AGES-Reykjavik Study.","authors":"Emma L Twait, Vilmundur Gudnason, Lenore J Launer, Lotte Gerritsen, Mirjam I Geerlings","doi":"10.1159/000545184","DOIUrl":"https://doi.org/10.1159/000545184","url":null,"abstract":"<p><strong>Introduction: </strong>Advancing age is associated with global brain atrophy. Cross-sectional studies have found sex differences in neuroanatomy; however, longitudinal studies assessing sex differences in neurodegeneration are currently scarce. The effects of age and sex on brain atrophy may not be uniform across the whole brain and may partially explain the sex differences observed in dementia. The current study aimed to examine sex differences in longitudinal atrophy patterns in gray and white matter regions in older adults.</p><p><strong>Methods: </strong>The study sample included 1480 individuals from the AGES-Reykjavik Study, a population-based cohort study, that underwent two MRI scans within an average of 5 years between assessments. Individuals were also followed-up for incident dementia diagnosis. Linear regression models were used to assess sex differences between mean differences in gray and white matter regions, correcting for age, education, baseline intracranial volume, baseline regional volumes, hypertension, body mass index, and APOE e4 allele status.</p><p><strong>Results: </strong>Men showed increased longitudinal atrophy in the total gray matter, as well as in the parietal cortex, cingulate cortex, caudate nucleus, brainstem, left cerebellum, precentral gyrus, putamen, globus pallidus, and orbitofrontal cortex. Whereas women exhibited greater atrophy over time in total white matter, but not in specific regions. No moderation was found between sex differences on incident dementia regarding atrophy patterns.</p><p><strong>Conclusions: </strong>While men show larger gray matter volumes cross-sectionally, their rates of atrophy over time are steeper compared to women. Sex differences in brain atrophy seem to be specifically detrimental in men in regions related to executive functioning, motor control, and emotion processing.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"1-15"},"PeriodicalIF":1.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625300","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":"Locus Coeruleus Sexual Dimorphism and Its Impact on Cognitive Impairment and Cortical Atrophy in Alzheimer's Disease.","authors":"Alessandro Galgani, Francesco Lombardo, Francesca Frijia, Marco Scotto, Gloria Tognoni, Nicola Pavese, Filippo Sean Giorgi","doi":"10.1159/000544882","DOIUrl":"10.1159/000544882","url":null,"abstract":"<p><strong>Introduction: </strong>Experimental data suggest sexual dimorphism in the Locus Coeruleus (LC), with females exhibiting higher neuronal count and noradrenergic activity. In Alzheimer's disease (AD), progressive LC dysfunction may contribute early to pathogenesis, and female sex is a key risk factor for AD. This study aimed to investigate if such sex differences exist in humans and whether they influence the relationship between LC degeneration and AD features, such as cortical atrophy and cognitive decline.</p><p><strong>Methods: </strong>Fifty-three healthy controls (HCs), 70 mild cognitive impaired (MCI) participants, and 29 Alzheimer's disease demented (ADD) patients underwent high-field brain MRI with LC-sensitive sequences following detailed neuropsychological and neurological assessments. LC integrity was measured using the LC contrast ratio (LCCR) parameter based on a previously published template approach.</p><p><strong>Results: </strong>Within the HC and MCI groups, females showed higher LCCR values than males. A significant sex effect was observed in the relationship between LC integrity and cortical volume in the frontotemporal cortices, with males showing a stronger association.</p><p><strong>Conclusion: </strong>LC structure and function may differ between sexes, influencing AD pathophysiology through distinct mechanisms. While this sexual dimorphism may have a minor role, it should be considered in clinical investigations and drug development research.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"1-14"},"PeriodicalIF":1.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516247","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":"Huntington's Disease in Hospitalized Patients Infected with SARS-CoV-2 in Brazil: Three-Year Update.","authors":"Jéssica Paula Martins, Juliana Mozer Sciani, Fernando Augusto Lima Marson","doi":"10.1159/000538170","DOIUrl":"10.1159/000538170","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Huntington's disease (HD) is considered a rare and fatal neurodegenerative disease; despite that, only one study has described the outcomes among individuals with HD and COVID-19. In this context, an epidemiological investigation was conducted in Brazil using data from Open-Data-SUS (&lt;ext-link ext-link-type=\"uri\" xlink:href=\"https://opendatasus.saude.gov.br/\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;https://opendatasus.saude.gov.br/&lt;/ext-link&gt;), a Brazilian open dataset encompassing demographic and clinical information of hospitalized patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;The study comprised 2,180,403 hospitalized patients due to COVID-19 in Brazil from December 29, 2019, to April 6, 2023. From the total original database, patients with HD and three control groups were selected (control 1 [CG-1] - hospitalized patients with COVID-19 and a neurological disorder [except those with HD], control 2 [CG-2] - hospitalized patients with COVID-19 and no comorbidities, and control 3 [CG-3] - hospitalized patients with COVID-19 except for those with HD). The study described the following characteristics of these patients: sex, age, race, place of residence, presence of nosocomial infection, clinical signs, comorbidities, use of antiviral medication for the flu, need for intensive care unit, need for mechanical ventilation support, discharge criteria, and outcome.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 60 patients with HD were enrolled, representing a prevalence of 2.8 per 100,000 inhabitants. Of these, 23 were men, 30 were aged between 25 and 60 years, 38 were White, 58 lived in urban areas, and two had a nosocomial infection. The main clinical signs presented were fever (N = 45), dyspnea (N = 45), peripheral oxygen saturation &lt;95% (N = 45), cough (N = 38), and respiratory discomfort (N = 37). The main comorbidities were cardiopathy (N = 13), asthma (N = 2), and chronic lung disease (N = 2). Four patients received antiviral medication for the flu. During hospitalization, 18 patients required admission to an intensive care unit, 10 used invasive mechanical ventilation, 42 used noninvasive mechanical ventilation, and eight did not use ventilatory support. Regarding outcomes, 36 patients were cured, 23 died due to COVID-19, and 1 died from a cause not associated with COVID-19. In the comparison of markers between patients with HD and the controls, the following significant associations were described: (CG-1) patients with HD were younger and presented fewer clinical signs and comorbidities; (CG-2) patients with HD were commonly female, older, presented fewer clinical signs, and had a higher chance of death (OR = 2.354 [95% CI = 1.395-3.973]); and (CG-3) patients with HD were more commonly female and presented fewer clinical signs and comorbidities.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Patients with HD can be considered an at-risk population due to the poor clinical outcomes compared to patients without comorbidities. E","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"1-18"},"PeriodicalIF":1.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468642","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":"A Review of Sex Differences in Neurodegeneration and Psychological Comorbidities in Multiple Sclerosis and Related Disorders.","authors":"Jelena Brasanac, Josephine Heine, Claudia Chien","doi":"10.1159/000544813","DOIUrl":"10.1159/000544813","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are chronic neuroinflammatory conditions that disproportionately affect women, with a 2:1 ratio in MS and up to 8.9:1 in NMOSD. Cognitive impairment is one of the earliest and most debilitating symptoms of MS, while mood disorders are common and significantly impact the quality of life and disease prognosis. Understanding sex differences in disease progression, particularly the potential differences in the mechanisms behind disability, is critical for advancing patient care.</p><p><strong>Summary: </strong>This review synthesizes current knowledge of sex-specific differences in MS and NMOSD, with a focus on neuroinflammation and neurodegeneration, as well as cognitive symptoms, and psychiatric comorbidities. The current state of research highlights the role of hormonal changes over the patient's lifespan, such as estrogen and testosterone, as well as their role in modulating neuroinflammatory responses and subsequent neurodegeneration.</p><p><strong>Key messages: </strong>Sex differences research in MS and NMOSD is scarce. Here, we discuss implications of disease monitoring and furthering knowledge in the field with a sex-specific lens, including recommendations for evaluating sex differences and personalized care in MS and NMOSD.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"1-15"},"PeriodicalIF":1.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458702","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":"Sex Differences for Social Determinants Associated with Lewy Body Dementia Onset and Diagnosis.","authors":"Ece Bayram, Kathryn A Wyman-Chick, Reilly Costello, Hamidreza Ghodsi, Charlotte S Rivera, Lisa Solomon, Joseph P M Kane, Irene Litvan","doi":"10.1159/000544772","DOIUrl":"10.1159/000544772","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple studies report sex and gender differences in Lewy body dementia (LBD); however, there is a paucity of research investigating social determinants associated with LBD.</p><p><strong>Methods: </strong>Participants with LBD (51 females, 79 males) and controls with similar age (64 females, 60 males) completed remote surveys assessing various social and demographic variables, and age at LBD onset for LBD group. Sex-stratified comparisons for LBD and control groups, and comparisons of females and males with LBD were done for social determinants. Sex differences for onset age were further analyzed with linear models adjusting for significantly differing social variables between the sexes.</p><p><strong>Results: </strong>LBD group had lower years of education, income, subjective social status than controls, with larger differences for males than females (p < 0.05 for all). Higher percentage of females with LBD was living alone (p = 0.016) and not married/partnered (p = 0.002) compared to males with LBD. Adjusting for social variables that differed between the sexes, females were younger at cognitive impairment onset (p = 0.037) and diagnosis (p = 0.032). For the overall cohort, being ethnoracial minoritized, sexual and gender minoritized, and having lower education quality were associated with younger age at symptom onset (p < 0.049 for all). For females, lower childhood subjective social status (p = 0.037), and for males, being ethnoracial minoritized (p < 0.001) and lower years of education (p = 0.031) were associated with younger age at diagnosis.</p><p><strong>Conclusion: </strong>Social determinants, even during childhood, can impact the LBD onset differently for females and males. Interactions between biological and social factors need to be investigated further with inclusive and diverse cohorts in LBD.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"1-13"},"PeriodicalIF":1.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449680","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":"Anti-Amyloid Drugs for Alzheimer's Disease: Considering the Role of Depression.","authors":"Beatriz Pozuelo Moyano, Leonardo Zullo, Olivier Rouaud, Pierre Vandel, Armin von Gunten, Gilles Allali","doi":"10.1159/000541783","DOIUrl":"10.1159/000541783","url":null,"abstract":"","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"1-14"},"PeriodicalIF":1.9,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794966","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":"Neurology of Aging: Adapting Neurology Provision for an Aging Population.","authors":"Patrick Stancu, Lisa Hentsch, Margitta Seeck, Dina Zekry, Christophe Graf, Vanessa Fleury, Frédéric Assal","doi":"10.1159/000540972","DOIUrl":"10.1159/000540972","url":null,"abstract":"<p><strong>Background: </strong>Over the past few decades, advances in the neurology of aging have been considerable and have led to a better understanding of the science of age-related neurological disorders. Likewise, it changed the perception of classical neurology practice, research, and the way of looking at age-related conditions. Neurological disorders are the most frequent cause of major disability in the elderly and account for almost half of the incapacitation occurring beyond age 65 and more than 90% of serious dependency. However, a number of neurological changes occur also in the absence of a specific disease, making the assessment and management of neurological complaints and findings a specific expertise.</p><p><strong>Summary: </strong>Maximizing success in clinical care of the elderly requires expertise in geriatric neurology, which includes an understanding of current research regarding aging and age-related neurological dysfunctions, and the ability to work with other geriatric healthcare providers. Although current therapies for neurodegenerative diseases mainly offer symptomatic relief without slowing progression, the landscape is evolving. Biomarkers of pathology and neuroimaging have continued to develop, with a significant impact on diagnosis and treatment. These advances have not only helped to improve our knowledge of disease pathophysiology but also disease stages, guiding symptomatic monitoring, and possible therapeutic options at a pre-symptomatic stage.</p><p><strong>Key messages: </strong>Neurological disorders are a leading cause of major disability and dependency in the elderly, underscoring the need for expertise in geriatric neurology for effective clinical care of this population. Although current therapies for neurodegenerative diseases primarily provide symptomatic relief without slowing disease progression, advancements in biomarkers and neuroimaging are significantly evolving. These advancements enhance our understanding of disease pathophysiology and stages, guiding symptomatic monitoring and potential therapeutic options at a pre-symptomatic stage. As knowledge about age-associated conditions is steadily rising and geriatric medicine gains further recognition, this article argues for a new focus on the role of neurologists in geriatric medicine, emphasizing the importance of integrating current research and collaborative care approaches in the management of elderly patients.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"1-7"},"PeriodicalIF":1.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381329","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":"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":1.9,"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":1.9,"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}