Ibrahim Abdu Wakawa, Umar Baba Musami, Suleiman Hamidu Kwairanga, Placidus Nwankuba Ogualili, Mohammed Yusuf Mahmood, Muhammad Abba Fugu, Mohammed Mala Gimba, Muktar Mohammed Allamin, Zaharadeen Umar Abbas, Muhammad Kawu Sunkani, Zainab Bukar Yaganami, Fatima Mustapha Kadau, Nasir Muhammad Sani, Peter Danmallam, Luka Nanjul, Larema Babazau, Zaid Muhammad, Baba Waru Goni, Babagana Kundi Machina, Celeste M. Karch, Chinedu Udeh-Momoh, Thomas K. Karikari, Chiadi U. Onyike, Mahmoud Bukar Maina
Dementia prevalence is increasing in sub-Saharan Africa, potentially due to population growth and aging. Resource-constrained settings such as Northeastern Nigeria face challenges in dementia management.
{"title":"Dementia in a resource-constrained sub-Saharan African setting: A comprehensive retrospective analysis of prevalence, risk factors, and management at the only neuropsychiatric facility in Northeastern Nigeria","authors":"Ibrahim Abdu Wakawa, Umar Baba Musami, Suleiman Hamidu Kwairanga, Placidus Nwankuba Ogualili, Mohammed Yusuf Mahmood, Muhammad Abba Fugu, Mohammed Mala Gimba, Muktar Mohammed Allamin, Zaharadeen Umar Abbas, Muhammad Kawu Sunkani, Zainab Bukar Yaganami, Fatima Mustapha Kadau, Nasir Muhammad Sani, Peter Danmallam, Luka Nanjul, Larema Babazau, Zaid Muhammad, Baba Waru Goni, Babagana Kundi Machina, Celeste M. Karch, Chinedu Udeh-Momoh, Thomas K. Karikari, Chiadi U. Onyike, Mahmoud Bukar Maina","doi":"10.1002/alz.14538","DOIUrl":"https://doi.org/10.1002/alz.14538","url":null,"abstract":"Dementia prevalence is increasing in sub-Saharan Africa, potentially due to population growth and aging. Resource-constrained settings such as Northeastern Nigeria face challenges in dementia management.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"33 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660312","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}
The presence of tau aggregates in and around the brain vasculature in Alzheimer's disease (AD) and tauopathies suggests its possible pathogenicity to cerebral endothelial cells (ECs).
{"title":"Fibrillar tau alters cerebral endothelial cell metabolism, vascular inflammatory activation, and barrier function in vitro and in vivo","authors":"Roberto Guzmán-Hernández, Silvia Fossati","doi":"10.1002/alz.70077","DOIUrl":"https://doi.org/10.1002/alz.70077","url":null,"abstract":"The presence of tau aggregates in and around the brain vasculature in Alzheimer's disease (AD) and tauopathies suggests its possible pathogenicity to cerebral endothelial cells (ECs).","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"70 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660621","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}
Apoorva Safai, William R Buckingham, Erin M Jonaitis, Rebecca E Langhough, Sterling C. Johnson, W. Ryan Powell, Amy J. Kind, Barbara B. Bendlin, Pallavi Tiwari
Neighborhood disadvantage has been shown to impact health and cognitive outcomes, while morphological similarity network (MSN) can elucidate structural morphological patterns underlying cognitive functions. We hypothesized MSNs could provide cortical patterns linked with neighborhood disadvantage and cognitive function, explaining the potential risk of cognitive impairment in disadvantaged neighborhoods.
{"title":"Association of neighborhood disadvantage with cognitive function and cortical disorganization in an unimpaired cohort: An exploratory study","authors":"Apoorva Safai, William R Buckingham, Erin M Jonaitis, Rebecca E Langhough, Sterling C. Johnson, W. Ryan Powell, Amy J. Kind, Barbara B. Bendlin, Pallavi Tiwari","doi":"10.1002/alz.70095","DOIUrl":"https://doi.org/10.1002/alz.70095","url":null,"abstract":"Neighborhood disadvantage has been shown to impact health and cognitive outcomes, while morphological similarity network (MSN) can elucidate structural morphological patterns underlying cognitive functions. We hypothesized MSNs could provide cortical patterns linked with neighborhood disadvantage and cognitive function, explaining the potential risk of cognitive impairment in disadvantaged neighborhoods.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"43 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660306","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}
Clayton Mansel, Diego R. Mazzotti, Ryan Townley, Mihaela E. Sardiu, Russell H. Swerdlow, Robyn A. Honea, Olivia J. Veatch
Phenotype clustering reduces patient heterogeneity and could be useful when designing precision clinical trials. We hypothesized that the onset of early cognitive decline in patients would exhibit variance predicated on the clinical history documented prior to an Alzheimer's disease (AD) diagnosis.
{"title":"Distinct medical and substance use histories associate with cognitive decline in Alzheimer's disease","authors":"Clayton Mansel, Diego R. Mazzotti, Ryan Townley, Mihaela E. Sardiu, Russell H. Swerdlow, Robyn A. Honea, Olivia J. Veatch","doi":"10.1002/alz.70017","DOIUrl":"https://doi.org/10.1002/alz.70017","url":null,"abstract":"Phenotype clustering reduces patient heterogeneity and could be useful when designing precision clinical trials. We hypothesized that the onset of early cognitive decline in patients would exhibit variance predicated on the clinical history documented prior to an Alzheimer's disease (AD) diagnosis.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"56 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660324","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}
Cellas A. Hayes, Christina B. Young, Carla Abdelnour, Alexis Reeves, Michelle C. Odden, Jeffrey Nirschl, Paul K. Crane, Kathleen L. Poston, Elizabeth C. Mormino, Kyan Younes
Alzheimer's disease neuropathologic change (ADNC), Lewy body disease (LBD), and vascular neuropathologies occur together. Previous studies have been limited by a large majority of participants with severe dementia or advanced stages of pathologies, which limits the detectability of cognitive effects from vascular neuropathologies.
{"title":"The impact of arteriolosclerosis on cognitive impairment in decedents without severe dementia from the National Alzheimer's Coordinating Center","authors":"Cellas A. Hayes, Christina B. Young, Carla Abdelnour, Alexis Reeves, Michelle C. Odden, Jeffrey Nirschl, Paul K. Crane, Kathleen L. Poston, Elizabeth C. Mormino, Kyan Younes","doi":"10.1002/alz.70059","DOIUrl":"https://doi.org/10.1002/alz.70059","url":null,"abstract":"Alzheimer's disease neuropathologic change (ADNC), Lewy body disease (LBD), and vascular neuropathologies occur together. Previous studies have been limited by a large majority of participants with severe dementia or advanced stages of pathologies, which limits the detectability of cognitive effects from vascular neuropathologies.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"200 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660543","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}
Vaibhav Tripathi, Joshua Fox-Fuller, Vincent Malotaux, Ana Baena, Nikole Bonillas Felix, Sergio Alvarez, David Aguillon, Francisco Lopera, David C. Somers, Yakeel T. Quiroz
Autosomal dominant Alzheimer's disease (ADAD) through genetic mutations can result in near complete expression of the disease. Tracking AD pathology development in an ADAD cohort of Presenilin-1 (PSEN1) E280A carriers’ mutation has allowed us to observe incipient tau tangles accumulation as early as 6 years prior to symptom onset.
{"title":"Connectome-based predictive modeling of brain pathology and cognition in autosomal dominant Alzheimer's disease","authors":"Vaibhav Tripathi, Joshua Fox-Fuller, Vincent Malotaux, Ana Baena, Nikole Bonillas Felix, Sergio Alvarez, David Aguillon, Francisco Lopera, David C. Somers, Yakeel T. Quiroz","doi":"10.1002/alz.70061","DOIUrl":"https://doi.org/10.1002/alz.70061","url":null,"abstract":"Autosomal dominant Alzheimer's disease (ADAD) through genetic mutations can result in near complete expression of the disease. Tracking AD pathology development in an ADAD cohort of Presenilin-1 (<i>PSEN1)</i> E280A carriers’ mutation has allowed us to observe incipient tau tangles accumulation as early as 6 years prior to symptom onset.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"183 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660602","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}
Selin Karakose, Martina Luchetti, Yannick Stephan, Angelina R. Sutin, Antonio Terracciano
Marital status is a potential risk/protective factor for adverse health outcomes. This study tested whether marital status was associated with dementia risk in older adults.
{"title":"Marital status and risk of dementia over 18 years: Surprising findings from the National Alzheimer's Coordinating Center","authors":"Selin Karakose, Martina Luchetti, Yannick Stephan, Angelina R. Sutin, Antonio Terracciano","doi":"10.1002/alz.70072","DOIUrl":"https://doi.org/10.1002/alz.70072","url":null,"abstract":"Marital status is a potential risk/protective factor for adverse health outcomes. This study tested whether marital status was associated with dementia risk in older adults.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"9 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660620","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}
Lisha Wang, Banesh Sooram, Rajnish Kumar, Sophia Schedin-Weiss, Lars O. Tjernberg, Bengt Winblad
In Alzheimer's disease (AD), tau undergoes abnormal post-translational modifications and aggregations. Impaired intracellular degradation pathways further exacerbate the accumulation of pathological tau. A new strategy – targeted protein degradation – recently emerged as a modality in drug discovery where bifunctional molecules bring the target protein close to the degradation machinery to promote clearance. Since 2016, this strategy has been applied to tau pathologies and attracted broad interest in academia and the pharmaceutical industry. However, a systematic review of recent studies on tau degradation mechanisms is lacking. Here we review tau degradation mechanisms (the ubiquitin–proteasome system and the autophagy–lysosome pathway), their dysfunction in AD, and tau-targeted degraders, such as proteolysis-targeting chimeras and autophagy-targeting chimeras. We emphasize the need for a continuous exploration of tau degradation mechanisms and provide a future perspective for developing tau-targeted degraders, encouraging researchers to work on new treatment options for AD patients.
{"title":"Tau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities","authors":"Lisha Wang, Banesh Sooram, Rajnish Kumar, Sophia Schedin-Weiss, Lars O. Tjernberg, Bengt Winblad","doi":"10.1002/alz.70048","DOIUrl":"https://doi.org/10.1002/alz.70048","url":null,"abstract":"In Alzheimer's disease (AD), tau undergoes abnormal post-translational modifications and aggregations. Impaired intracellular degradation pathways further exacerbate the accumulation of pathological tau. A new strategy – targeted protein degradation – recently emerged as a modality in drug discovery where bifunctional molecules bring the target protein close to the degradation machinery to promote clearance. Since 2016, this strategy has been applied to tau pathologies and attracted broad interest in academia and the pharmaceutical industry. However, a systematic review of recent studies on tau degradation mechanisms is lacking. Here we review tau degradation mechanisms (the ubiquitin–proteasome system and the autophagy–lysosome pathway), their dysfunction in AD, and tau-targeted degraders, such as proteolysis-targeting chimeras and autophagy-targeting chimeras. We emphasize the need for a continuous exploration of tau degradation mechanisms and provide a future perspective for developing tau-targeted degraders, encouraging researchers to work on new treatment options for AD patients.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"34 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660319","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}
Eloise Berson, Brett M. Frye, Chandresh R. Gajera, Geetha Saarunya, Amalia Perna, Thanaphong Phongpreecha, Sayane Shome, Jacob D. Negrey, Nima Aghaeepour, Thomas J. Montine, Suzanne Craft, Thomas C. Register, Carol A. Shively
Diet quality mediates aging-related risks of cognitive decline, neurodegeneration, and Alzheimer's disease (AD) through poorly defined mechanisms.
{"title":"Mediterranean vs. Western diet effects on the primate cerebral cortical pre-synaptic proteome: Relationships with the transcriptome and multi-system phenotypes","authors":"Eloise Berson, Brett M. Frye, Chandresh R. Gajera, Geetha Saarunya, Amalia Perna, Thanaphong Phongpreecha, Sayane Shome, Jacob D. Negrey, Nima Aghaeepour, Thomas J. Montine, Suzanne Craft, Thomas C. Register, Carol A. Shively","doi":"10.1002/alz.70041","DOIUrl":"https://doi.org/10.1002/alz.70041","url":null,"abstract":"Diet quality mediates aging-related risks of cognitive decline, neurodegeneration, and Alzheimer's disease (AD) through poorly defined mechanisms.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"26 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660320","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}
Ping Bai, Prasenjit Mondal, Yan Liu, Ashley Gomm, Claire Suen, Liuyue Yang, Biyue Zhu, Haoqi Sun, Chongzhao Ran, Shiqian Shen, Rudolph E. Tanzi, Can Zhang, Changning Wang
Alzheimer's disease (AD) is characterized by amyloid pathology and neuroinflammation, leading to cognitive decline. Targeting histone deacetylase-11 (HDAC11) offers a novel therapeutic strategy due to its role in immune regulation.
{"title":"HDAC11 displays neuropathological alterations and offers as a novel drug target for Alzheimer's disease","authors":"Ping Bai, Prasenjit Mondal, Yan Liu, Ashley Gomm, Claire Suen, Liuyue Yang, Biyue Zhu, Haoqi Sun, Chongzhao Ran, Shiqian Shen, Rudolph E. Tanzi, Can Zhang, Changning Wang","doi":"10.1002/alz.14616","DOIUrl":"https://doi.org/10.1002/alz.14616","url":null,"abstract":"Alzheimer's disease (AD) is characterized by amyloid pathology and neuroinflammation, leading to cognitive decline. Targeting histone deacetylase-11 (HDAC11) offers a novel therapeutic strategy due to its role in immune regulation.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"25 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660317","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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