Pub Date : 2026-02-05DOI: 10.1186/s13024-026-00925-5
Aram Aslanyan, Martha S Foiani, Tatiana A Giovannucci, Eric McDade, Karen E Duff, Catherine J Mummery, Michael Schöll, Kristin R Wildsmith, Ross W Paterson
{"title":"Targeting tau in Alzheimer's Disease: rationale, approach and challenges.","authors":"Aram Aslanyan, Martha S Foiani, Tatiana A Giovannucci, Eric McDade, Karen E Duff, Catherine J Mummery, Michael Schöll, Kristin R Wildsmith, Ross W Paterson","doi":"10.1186/s13024-026-00925-5","DOIUrl":"https://doi.org/10.1186/s13024-026-00925-5","url":null,"abstract":"","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-04DOI: 10.1186/s13024-026-00932-6
Koen Kuipers, Sam Vanherle, Kirsten Poelmans, Esther Wolfs, Jeroen Bogie, Tim Vangansewinkel
{"title":"Lipid alterations in hereditary peripheral neuropathies: common mechanisms in disease heterogeneity?","authors":"Koen Kuipers, Sam Vanherle, Kirsten Poelmans, Esther Wolfs, Jeroen Bogie, Tim Vangansewinkel","doi":"10.1186/s13024-026-00932-6","DOIUrl":"https://doi.org/10.1186/s13024-026-00932-6","url":null,"abstract":"","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1186/s13024-026-00928-2
Kristeen A Pareja-Navarro, Christina D King, Grant Kauwe, Yani Y Ngwala, Doyle Lokitiyakul, Ivy Wong, Aaryan Vira, Yaofu Liu, Jackson H Chen, Mahima Sharma, Gabriel Navarro, Olfat Malak, Chuankai Zhou, Birgit Schilling, Tara E Tracy
{"title":"Tau oligomers modulate synapse fate by eliciting progressive bipartite synapse dysregulation and synapse loss.","authors":"Kristeen A Pareja-Navarro, Christina D King, Grant Kauwe, Yani Y Ngwala, Doyle Lokitiyakul, Ivy Wong, Aaryan Vira, Yaofu Liu, Jackson H Chen, Mahima Sharma, Gabriel Navarro, Olfat Malak, Chuankai Zhou, Birgit Schilling, Tara E Tracy","doi":"10.1186/s13024-026-00928-2","DOIUrl":"10.1186/s13024-026-00928-2","url":null,"abstract":"","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":" ","pages":""},"PeriodicalIF":17.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDComplement dysregulation is increasingly recognized in Alzheimer's disease (AD). However, the temporal profile of complement alterations preceding AD onset and their distinction from age-related immune changes remain poorly defined. Clarifying these dynamics could provide insights into AD pathogenesis and identify systemic factors that predict disease onset and progression.METHODSWe conducted a study involving two cohorts: a longitudinal cohort (n = 235; all cognitively normal at baseline) and a cross-sectional cohort (n = 323; including 53 with AD, 54 with vascular dementia, 51 with Parkinson's disease dementia, 56 with behavioral variant frontotemporal dementia, and 52 with dementia with Lewy bodies). Plasma levels of 14 complement factors were assessed every 2 years over a 10-year follow-up period in the longitudinal cohort and once in the cross-sectional cohort.RESULTSIn the longitudinal cohort, aging was accompanied by gradual reductions in C4, C4b, Factor I, and Properdin and by increases in Factor D. These changes were more pronounced in individuals who subsequently developed AD. Importantly, this pattern of complement alterations was detectable during the preclinical and clinical phases of AD but was not observed in other dementias. In the cross-sectional cohort, the same complement profile was specific to AD and distinguished it from other dementia subtypes.CONCLUSIONSThe results of this study indicate an AD-specific peripheral complement signature associated with disease development, highlighting complement factors as critical immune mediators that link aging and AD. This signature implicates complement factors as promising systemic markers for early detection and potential therapeutic targeting in preclinical AD.
{"title":"Systemic complement factors in aging, Alzheimer's disease and other dementias: a longitudinal study over 10 years.","authors":"Xiaofeng Fu,Huimin Cai,Shuiyue Quan,Weiyun Zhang,Yumei Geng,Qing Tian,Ziye Ren,Yinghao Xu,Chengyu An,Jiaqi Li,Changbiao Chu,Wei Wang,Yana Pang,QianQian Wang,Lu Lu,Qi Wang,Yan Li,Fangyu Li,Shuya Nie,Longfei Jia","doi":"10.1186/s13024-026-00927-3","DOIUrl":"https://doi.org/10.1186/s13024-026-00927-3","url":null,"abstract":"BACKGROUNDComplement dysregulation is increasingly recognized in Alzheimer's disease (AD). However, the temporal profile of complement alterations preceding AD onset and their distinction from age-related immune changes remain poorly defined. Clarifying these dynamics could provide insights into AD pathogenesis and identify systemic factors that predict disease onset and progression.METHODSWe conducted a study involving two cohorts: a longitudinal cohort (n = 235; all cognitively normal at baseline) and a cross-sectional cohort (n = 323; including 53 with AD, 54 with vascular dementia, 51 with Parkinson's disease dementia, 56 with behavioral variant frontotemporal dementia, and 52 with dementia with Lewy bodies). Plasma levels of 14 complement factors were assessed every 2 years over a 10-year follow-up period in the longitudinal cohort and once in the cross-sectional cohort.RESULTSIn the longitudinal cohort, aging was accompanied by gradual reductions in C4, C4b, Factor I, and Properdin and by increases in Factor D. These changes were more pronounced in individuals who subsequently developed AD. Importantly, this pattern of complement alterations was detectable during the preclinical and clinical phases of AD but was not observed in other dementias. In the cross-sectional cohort, the same complement profile was specific to AD and distinguished it from other dementia subtypes.CONCLUSIONSThe results of this study indicate an AD-specific peripheral complement signature associated with disease development, highlighting complement factors as critical immune mediators that link aging and AD. This signature implicates complement factors as promising systemic markers for early detection and potential therapeutic targeting in preclinical AD.","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"47 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1186/s13024-025-00919-9
Gabriella A Perez,Zoe Lai,George A Edwards Iii,Jacob M Dundee,Shannon N Leahy,Chuangye Qi,Yanyan Qi,Ye-Jin Park,Tzu-Chiao Lu,M Danish Uddin,Rong Zhao,Hui Zheng,Hongjie Li,Joanna L Jankowsky
{"title":"Neuronal subtype governs amyloid structure, cellular response, and cognitive outcome in genetically targeted APP mouse models.","authors":"Gabriella A Perez,Zoe Lai,George A Edwards Iii,Jacob M Dundee,Shannon N Leahy,Chuangye Qi,Yanyan Qi,Ye-Jin Park,Tzu-Chiao Lu,M Danish Uddin,Rong Zhao,Hui Zheng,Hongjie Li,Joanna L Jankowsky","doi":"10.1186/s13024-025-00919-9","DOIUrl":"https://doi.org/10.1186/s13024-025-00919-9","url":null,"abstract":"","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"15 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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