Rodrigo Cánovas, Christopher J. Fowler, Azadeh Feizpour, Vincent Dóre, Pierrick Bourgeat, Ziad S. Saad, Gallen Triana-Baltzer, Hartmuth C. Kolb, Manu Vandijck, Gwendlyn Kollmorgen, Clara Quijano-Rubio, Jurgen Fripp, Simon Laws, Anthony W. Bannon, Kaj Blennow, Henrik Zetterberg, Stephanie Rainey-Smith, Sulantha Mathotaarachchi, Christopher C. Rowe, Colin L. Masters, James D. Doecke
With increased uptake in disease-modifying treatments for amyloid beta (Aβ) removal, it is important to measure performance of highly sensitive plasma biomarkers to detect the presence of Aβ and tau in cognitively impaired populations.
{"title":"Plasma biomarker progression across the Alzheimer's disease amyloid beta and tau positron emission tomography trajectories","authors":"Rodrigo Cánovas, Christopher J. Fowler, Azadeh Feizpour, Vincent Dóre, Pierrick Bourgeat, Ziad S. Saad, Gallen Triana-Baltzer, Hartmuth C. Kolb, Manu Vandijck, Gwendlyn Kollmorgen, Clara Quijano-Rubio, Jurgen Fripp, Simon Laws, Anthony W. Bannon, Kaj Blennow, Henrik Zetterberg, Stephanie Rainey-Smith, Sulantha Mathotaarachchi, Christopher C. Rowe, Colin L. Masters, James D. Doecke","doi":"10.1002/alz.71145","DOIUrl":"https://doi.org/10.1002/alz.71145","url":null,"abstract":"With increased uptake in disease-modifying treatments for amyloid beta (Aβ) removal, it is important to measure performance of highly sensitive plasma biomarkers to detect the presence of Aβ and tau in cognitively impaired populations.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"73 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146298","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}
Elise Kinyanjui, Renee C. Groechel, Valerie Morrill, Keenan A. Walker, Anna M. Kucharska-Newton, Thomas H. Mosley, Silvia Koton, David S. Knopman, Jordan Weiss, Rebecca F. Gottesman, Marco Egle
Understanding comorbidities’ combined impacts on dementia risk may offer a more comprehensive understanding of individuals’ risk. Using machine-learning, we grouped individuals with similar midlife risk profiles into clusters and explored associations with dementia risk.
{"title":"The influence of midlife morbidity clusters on dementia risk: The ARIC study","authors":"Elise Kinyanjui, Renee C. Groechel, Valerie Morrill, Keenan A. Walker, Anna M. Kucharska-Newton, Thomas H. Mosley, Silvia Koton, David S. Knopman, Jordan Weiss, Rebecca F. Gottesman, Marco Egle","doi":"10.1002/alz.71110","DOIUrl":"https://doi.org/10.1002/alz.71110","url":null,"abstract":"Understanding comorbidities’ combined impacts on dementia risk may offer a more comprehensive understanding of individuals’ risk. Using machine-learning, we grouped individuals with similar midlife risk profiles into clusters and explored associations with dementia risk.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"45 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146295","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}
Deirdre M. O'Shea, Devi Dhanekula, Swati Kumar, Lily Wang, Lisa Wiese, Tatjana Rundek, James E. Galvin
INTRODUCTION Epigenetic assays may support non‐invasive dementia risk stratification; community views on willingness and implementation remain under‐characterized. METHODS In a survey of 425 adults ≥50 years old, we assessed the willingness for a hypothetical epigenetic test, implementation preferences, reactions to a high‐risk result, behavior‐change intentions, and reasons for not testing using multivariable models. RESULTS Overall, 82.1% showed a willingness. Health literacy (odds ratio [OR] = 2.61) and Alzheimer's disease (AD) concern (OR = 2.06) increased that willingness; doctor dependence decreased it (OR = 0.62). The top drivers were perceived to be accuracy and speed. The preferred modality was a combination of biomarker and cognitive over biomarker‐only. Intended changes prioritized alcohol reduction, then diet, exercise, cognitive activity. Risk worry and insurance concerns exceeded stigma; higher literacy related to lower stigma, and epigenetics familiarity and AD worry related to higher insurance concern. The reasons for not testing were data privacy/accuracy concerns, logistics/costs, and needles. DISCUSSION Findings support emphasizing test accuracy, turnaround, and governance/legal information when implementing DNAm testing for dementia risk.
{"title":"Community perspectives on epigenetic dementia risk testing: Willingness, implementation preferences, and reasons for not testing in midlife and older adults","authors":"Deirdre M. O'Shea, Devi Dhanekula, Swati Kumar, Lily Wang, Lisa Wiese, Tatjana Rundek, James E. Galvin","doi":"10.1002/alz.71094","DOIUrl":"https://doi.org/10.1002/alz.71094","url":null,"abstract":"INTRODUCTION Epigenetic assays may support non‐invasive dementia risk stratification; community views on willingness and implementation remain under‐characterized. METHODS In a survey of 425 adults ≥50 years old, we assessed the willingness for a hypothetical epigenetic test, implementation preferences, reactions to a high‐risk result, behavior‐change intentions, and reasons for not testing using multivariable models. RESULTS Overall, 82.1% showed a willingness. Health literacy (odds ratio [OR] = 2.61) and Alzheimer's disease (AD) concern (OR = 2.06) increased that willingness; doctor dependence decreased it (OR = 0.62). The top drivers were perceived to be accuracy and speed. The preferred modality was a combination of biomarker and cognitive over biomarker‐only. Intended changes prioritized alcohol reduction, then diet, exercise, cognitive activity. Risk worry and insurance concerns exceeded stigma; higher literacy related to lower stigma, and epigenetics familiarity and AD worry related to higher insurance concern. The reasons for not testing were data privacy/accuracy concerns, logistics/costs, and needles. DISCUSSION Findings support emphasizing test accuracy, turnaround, and governance/legal information when implementing DNAm testing for dementia risk.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"34 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122141","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}
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by synaptic loss, as a key pathological feature in its early stages. Recent studies have highlighted the central role of microglia–complement interactions in synaptic pruning. This interaction exhibits significant spatial heterogeneity in AD, with activation patterns and functional manifestations varying across different brain regions and stages of disease. Therefore, this article systematically reviews the synergistic mechanisms of microglia and the complement system in physiological synaptic pruning. Additionally, the dynamic evolution of the complement–immune network during disease progression is analyzed, and the amplifying effect of genetic factors on the spatial heterogeneity of synaptic pruning is explored. Furthermore, current treatment strategies from both Western medicine and traditional Chinese medicine are discussed, emphasizing the potential value of combining these approaches for intervening in synaptic loss in AD.
{"title":"Spatial heterogeneity in microglia-complement crosstalk: Implications for synaptic pruning in Alzheimer's disease","authors":"Qiuyan Ye, Wei Gao, Jiaping Feng, Xue Li, Jianhui Li, Fengge Yang, Linqing Li, Mingsheng Zi, Xinkai Wu, Hainan Gao, Honglin Li","doi":"10.1002/alz.71185","DOIUrl":"https://doi.org/10.1002/alz.71185","url":null,"abstract":"Alzheimer's disease (AD) is a neurodegenerative disorder characterized by synaptic loss, as a key pathological feature in its early stages. Recent studies have highlighted the central role of microglia–complement interactions in synaptic pruning. This interaction exhibits significant spatial heterogeneity in AD, with activation patterns and functional manifestations varying across different brain regions and stages of disease. Therefore, this article systematically reviews the synergistic mechanisms of microglia and the complement system in physiological synaptic pruning. Additionally, the dynamic evolution of the complement–immune network during disease progression is analyzed, and the amplifying effect of genetic factors on the spatial heterogeneity of synaptic pruning is explored. Furthermore, current treatment strategies from both Western medicine and traditional Chinese medicine are discussed, emphasizing the potential value of combining these approaches for intervening in synaptic loss in AD.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"117 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115813","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}
Angela K. Haskell, Joshua A. Kulas, William E. Carter, June Javens-Wolfe, Raven Dance Hinkel, Mustapha Moussaif, Jacob S. Smiley, Olivia Lazaro, Sylvia Robertson, Alan D. Palkowitz, Bruce T. Lamb, Timothy I. Richardson, Jeffrey L. Dage, Shaoyou Chu, Travis Johnson, Louis F. Stancato, Abdul Qadir Syed
INTRODUCTION
Microglia are macrophage-like brain resident immune cells known to express numerous Alzheimer's disease risk genes. Here we generated a human induced pluripotent stem cell (iPSC) derived microglia cell culture model for use in neuroimmune modeling and therapeutic testing.
METHODS
We generated iPSC lines using episomal reprogramming for subsequent stepwise differentiation of iPSC-derived microglia (iMG) without commercial kits. We characterized the responses of this model to immunogenic stimuli and recombinant TREM2 antibodies.
RESULTS
The iMG expressed several key microglia signature genes and are morphologically and transcriptionally dynamic. iMG rapidly phagocytosed myelin debris and strongly changed expression of lipid homeostasis genes. iMG expressed TREM2 and increased TREM2 levels in response to IL-4. Recombinant TREM2 antibody treatment impaired iMG myelin phagocytosis and upregulated chemokines.
DISCUSSION
We validated our iMG model system for the evaluation of biological responses of human microglia-like cells to stimuli and pharmacological agents for their transcriptional and functional impacts.
{"title":"Generation and characterization of iPSC-derived microglia for in vitro modeling of stimuli-specific neuroimmune responses","authors":"Angela K. Haskell, Joshua A. Kulas, William E. Carter, June Javens-Wolfe, Raven Dance Hinkel, Mustapha Moussaif, Jacob S. Smiley, Olivia Lazaro, Sylvia Robertson, Alan D. Palkowitz, Bruce T. Lamb, Timothy I. Richardson, Jeffrey L. Dage, Shaoyou Chu, Travis Johnson, Louis F. Stancato, Abdul Qadir Syed","doi":"10.1002/alz.71117","DOIUrl":"10.1002/alz.71117","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Microglia are macrophage-like brain resident immune cells known to express numerous Alzheimer's disease risk genes. Here we generated a human induced pluripotent stem cell (iPSC) derived microglia cell culture model for use in neuroimmune modeling and therapeutic testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We generated iPSC lines using episomal reprogramming for subsequent stepwise differentiation of iPSC-derived microglia (iMG) without commercial kits. We characterized the responses of this model to immunogenic stimuli and recombinant TREM2 antibodies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The iMG expressed several key microglia signature genes and are morphologically and transcriptionally dynamic. iMG rapidly phagocytosed myelin debris and strongly changed expression of lipid homeostasis genes. iMG expressed TREM2 and increased TREM2 levels in response to IL-4. Recombinant TREM2 antibody treatment impaired iMG myelin phagocytosis and upregulated chemokines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>We validated our iMG model system for the evaluation of biological responses of human microglia-like cells to stimuli and pharmacological agents for their transcriptional and functional impacts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 2","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alejandra O. Morcillo-Nieto, Mateus Rozalem-Aranha, Lucia Maure-Blesa, Íñigo Rodríguez-Baz, José Enrique Arriola-Infante, Maria Franquesa-Mullerat, Sara E. Zsadanyi, Lídia Vaqué-Alcázar, José Allende Parra, Zili Zhao, Javier Arranz, Laura Videla, Isabel Barroeta, Laura Del Hoyo Soriano, Bessy Benejam, Susana Fernández, Aida Sanjuan Hernandez, Lucia Pertierra, Sandra Giménez, Daniel Alcolea, Olivia Belbin, Alberto Lleó, María Carmona-Iragui, Juan Fortea, Alexandre Bejanin
INTRODUCTION
White matter hyperintensities (WMH) are common in Down syndrome (DS), yet their longitudinal evolution and associations with Alzheimer's disease (AD) remain unclear.
METHODS
Longitudinal MRI study, including 80 DS adults and 53 euploid controls. WMH were segmented on serial FLAIR using a longitudinal pipeline. We assessed the effects of demographic, genetic factors, AD clinical stage, AD-related fluid, and cerebrovascular biomarkers on annual WMH volume changes.
RESULTS
In DS, annual WMH changes were relatively stable until age 40, and then exhibited fluctuations, with a significant decrease at the group level. Declines were larger in symptomatic cases, particularly in periventricular and fronto-parieto-occipital regions. Higher baseline WMH and microbleeds presence related to greater WMH reduction. Visual ratings and adjustment for white matter volume supported the robustness of the results.
DISCUSSION
WMH trajectories were heterogeneous in DS and declined over time with AD symptoms. This unexpected reduction may reflect different underlying pathological processes, including neurodegeneration or neuroinflammation.
{"title":"Temporal dynamics of white matter hyperintensities related to Alzheimer's disease in adults with Down syndrome","authors":"Alejandra O. Morcillo-Nieto, Mateus Rozalem-Aranha, Lucia Maure-Blesa, Íñigo Rodríguez-Baz, José Enrique Arriola-Infante, Maria Franquesa-Mullerat, Sara E. Zsadanyi, Lídia Vaqué-Alcázar, José Allende Parra, Zili Zhao, Javier Arranz, Laura Videla, Isabel Barroeta, Laura Del Hoyo Soriano, Bessy Benejam, Susana Fernández, Aida Sanjuan Hernandez, Lucia Pertierra, Sandra Giménez, Daniel Alcolea, Olivia Belbin, Alberto Lleó, María Carmona-Iragui, Juan Fortea, Alexandre Bejanin","doi":"10.1002/alz.71157","DOIUrl":"10.1002/alz.71157","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>White matter hyperintensities (WMH) are common in Down syndrome (DS), yet their longitudinal evolution and associations with Alzheimer's disease (AD) remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Longitudinal MRI study, including 80 DS adults and 53 euploid controls. WMH were segmented on serial FLAIR using a longitudinal pipeline. We assessed the effects of demographic, genetic factors, AD clinical stage, AD-related fluid, and cerebrovascular biomarkers on annual WMH volume changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In DS, annual WMH changes were relatively stable until age 40, and then exhibited fluctuations, with a significant decrease at the group level. Declines were larger in symptomatic cases, particularly in periventricular and fronto-parieto-occipital regions. Higher baseline WMH and microbleeds presence related to greater WMH reduction. Visual ratings and adjustment for white matter volume supported the robustness of the results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>WMH trajectories were heterogeneous in DS and declined over time with AD symptoms. This unexpected reduction may reflect different underlying pathological processes, including neurodegeneration or neuroinflammation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 2","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tugce Duran, Murat Bilgel, Yang An, Sridhar Kandala, Christos Davatzikos, Bennett A. Landman, Guray Erus, Abhay Moghekar, Luigi Ferrucci, Keenan A. Walker, Susan M. Resnick
INTRODUCTION
This study longitudinally examined 154 magnetic resonance imaging (MRI) biomarkers in cognitively normal (CN) individuals to identify structural brain changes most strongly associated with subsequent cognitive impairment (SI).
METHODS
We analyzed 509 Baltimore Longitudinal Study of Aging participants (age ≥ 50, CN at baseline) with longitudinal cognitive and 3T MRI (T1/T2-weighted scans and diffusion tensor imaging) data. MRI biomarker associations with SI status were analyzed, adjusting for confounders and stratifying by sex and amyloid beta (Aβ) status.
RESULTS
Participants who developed SI over 4.6 years’ follow-up showed greater longitudinal changes in white matter (WM) integrity, particularly in the corpus callosum, cingulum bundle, and inferior fronto-occipital fasciculus, compared to CN-stable. To a lesser degree, we also observed temporal thinning and atrophy linked to SI. These associations were amplified among males and amyloid-positive individuals.
DISCUSSION
Longitudinal alterations in WM microstructural integrity were most strongly associated with future impairment, highlighting the importance of early WM changes in the development of MCI and dementia.
{"title":"An MRI-based macro- and microstructural neuroimaging-wide association study of subsequent cognitive impairment","authors":"Tugce Duran, Murat Bilgel, Yang An, Sridhar Kandala, Christos Davatzikos, Bennett A. Landman, Guray Erus, Abhay Moghekar, Luigi Ferrucci, Keenan A. Walker, Susan M. Resnick","doi":"10.1002/alz.71135","DOIUrl":"10.1002/alz.71135","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study longitudinally examined 154 magnetic resonance imaging (MRI) biomarkers in cognitively normal (CN) individuals to identify structural brain changes most strongly associated with subsequent cognitive impairment (SI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We analyzed 509 Baltimore Longitudinal Study of Aging participants (age ≥ 50, CN at baseline) with longitudinal cognitive and 3T MRI (T1/T2-weighted scans and diffusion tensor imaging) data. MRI biomarker associations with SI status were analyzed, adjusting for confounders and stratifying by sex and amyloid beta (Aβ) status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Participants who developed SI over 4.6 years’ follow-up showed greater longitudinal changes in white matter (WM) integrity, particularly in the corpus callosum, cingulum bundle, and inferior fronto-occipital fasciculus, compared to CN-stable. To a lesser degree, we also observed temporal thinning and atrophy linked to SI. These associations were amplified among males and amyloid-positive individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Longitudinal alterations in WM microstructural integrity were most strongly associated with future impairment, highlighting the importance of early WM changes in the development of MCI and dementia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 2","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12865317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah F Giardina,Alexander Culver,Chandrama Ahmed,Christian Mirescu,Adrian L Oblak,Jared Brosch,W Brent Clayton,Jeffrey L Dage,Bruce T Lamb,Timothy I Richardson,Derek Small,Alan D Palkowitz
Alzheimer's disease (AD) research has entered a new era where public-private partnerships are reigniting the pursuit of disease-modifying therapies targeting mechanisms beyond amyloid and tau. This perspective outlines how Monument Biosciences was founded to advance novel therapies by translating National Institutes of Health (NIH) -supported discoveries from the TaRget Enablement to Accelerate Therapy Development for AD (TREAT-AD) and the Model Organism Development and Evaluation for Late-onset AD (MODEL-AD) consortia into a venture-backed pipeline focused on neuroinflammation. Monument Bio strategically builds on genetic validation and high-quality, nondilutive-funded research and serves as a case study in how academic research can reduce risk in early-stage biotech development to advance novel therapies. The company exemplifies a novel academic-startup collaboration model, emphasizing robust biomarker strategies to streamline clinical development. Aligned with the framework presented by Richardson et al., in this issue, this approach supports a new generation of neuroscience companies grounded in open science, strong target validation, and disease-relevant endpoints. HIGHLIGHTS: The Alzheimer's field is poised for next-generation therapies beyond amyloid and tau. Monument Bio translates National Institutes of Health (NIH)-supported science into a venture-backed Alzheimer's pipeline. TaRget Enablement to Accelerate Therapy Development for AD (TREAT-AD) and Model Organism Development and Evaluation for Late-onset AD (MODEL-AD) de-risk programs with validated assays, probes, and biomarker tools. Monument Bio shows how TREAT-AD's Target Enabling Packages (TEPs) enable difficult targets. Integrated biomarkers enable predictive translation, faster approval, and investment rationale.
{"title":"From consortia discovery to biotech creation: An innovative approach to next-gen Alzheimer's drugs.","authors":"Sarah F Giardina,Alexander Culver,Chandrama Ahmed,Christian Mirescu,Adrian L Oblak,Jared Brosch,W Brent Clayton,Jeffrey L Dage,Bruce T Lamb,Timothy I Richardson,Derek Small,Alan D Palkowitz","doi":"10.1002/alz.71165","DOIUrl":"https://doi.org/10.1002/alz.71165","url":null,"abstract":"Alzheimer's disease (AD) research has entered a new era where public-private partnerships are reigniting the pursuit of disease-modifying therapies targeting mechanisms beyond amyloid and tau. This perspective outlines how Monument Biosciences was founded to advance novel therapies by translating National Institutes of Health (NIH) -supported discoveries from the TaRget Enablement to Accelerate Therapy Development for AD (TREAT-AD) and the Model Organism Development and Evaluation for Late-onset AD (MODEL-AD) consortia into a venture-backed pipeline focused on neuroinflammation. Monument Bio strategically builds on genetic validation and high-quality, nondilutive-funded research and serves as a case study in how academic research can reduce risk in early-stage biotech development to advance novel therapies. The company exemplifies a novel academic-startup collaboration model, emphasizing robust biomarker strategies to streamline clinical development. Aligned with the framework presented by Richardson et al., in this issue, this approach supports a new generation of neuroscience companies grounded in open science, strong target validation, and disease-relevant endpoints. HIGHLIGHTS: The Alzheimer's field is poised for next-generation therapies beyond amyloid and tau. Monument Bio translates National Institutes of Health (NIH)-supported science into a venture-backed Alzheimer's pipeline. TaRget Enablement to Accelerate Therapy Development for AD (TREAT-AD) and Model Organism Development and Evaluation for Late-onset AD (MODEL-AD) de-risk programs with validated assays, probes, and biomarker tools. Monument Bio shows how TREAT-AD's Target Enabling Packages (TEPs) enable difficult targets. Integrated biomarkers enable predictive translation, faster approval, and investment rationale.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"1 1 1","pages":"e71165"},"PeriodicalIF":14.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089111","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}
Dean A Regier, Jean O Taylor, Astoria Ho, Soo Borson, Anne M Turner
Introduction: Evidence is limited on preferences of persons with cognitive decline and their care partners (CPs) regarding care. Our aim was to identify preferences and preference evolution for transitions in supportive care.
Methods: We conducted a discrete choice experiment (DCE) (repeated measures baseline, 6-months) with older adults with mild cognitive impairment or mild to moderate dementia and CPs. Tasks were anchored to health states describing progressive memory and function decline. Split-sample mixed logit models estimated part-worth utilities.
Results: Baseline DCEs were completed by 131 cognitively impaired older adults and 137 CPs; 118 and 132 completed 6-month DCEs. At both timepoints, respondents preferred in-home care with moderate support when considering moderate or severe cognitive impairment. As impairment worsened, the acceptability of assisted living increased, especially among CPs.
Discussion: Persons with cognitive decline engaged in future-oriented decisions. Preferences were stable across time for both samples, and assisted living was more acceptable for CPs.
{"title":"Care preferences for persons with cognitive impairment: A discrete choice experiment.","authors":"Dean A Regier, Jean O Taylor, Astoria Ho, Soo Borson, Anne M Turner","doi":"10.1002/alz.71107","DOIUrl":"10.1002/alz.71107","url":null,"abstract":"<p><strong>Introduction: </strong>Evidence is limited on preferences of persons with cognitive decline and their care partners (CPs) regarding care. Our aim was to identify preferences and preference evolution for transitions in supportive care.</p><p><strong>Methods: </strong>We conducted a discrete choice experiment (DCE) (repeated measures baseline, 6-months) with older adults with mild cognitive impairment or mild to moderate dementia and CPs. Tasks were anchored to health states describing progressive memory and function decline. Split-sample mixed logit models estimated part-worth utilities.</p><p><strong>Results: </strong>Baseline DCEs were completed by 131 cognitively impaired older adults and 137 CPs; 118 and 132 completed 6-month DCEs. At both timepoints, respondents preferred in-home care with moderate support when considering moderate or severe cognitive impairment. As impairment worsened, the acceptability of assisted living increased, especially among CPs.</p><p><strong>Discussion: </strong>Persons with cognitive decline engaged in future-oriented decisions. Preferences were stable across time for both samples, and assisted living was more acceptable for CPs.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 2","pages":"e71107"},"PeriodicalIF":11.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12865324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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