Citations 2
Cortical asymmetry in autosomal dominant Alzheimer’s disease progression
Pérez-Millan, Agnès , Falgàs, Neus , Borrego-Écija, Sergi, Antonell, Anna, Fernández-Villullas, Guadalupe, Esteller-Gauxax, Diana, Tort-Merino, Adrià, Bargalló, Núria, Balasa, Mircea, Lladó, Albert, Chrem, Patricio, Day, Gregory S. , Devenney, Emma , Huey, Edward D. , Ikeuchi, Takeshi, Jucker, Mathias, Roh, Jee Hoon , Vitali, Paolo , Ortíz, Ana Luisa Sosa, Llibre-Guerra, Jorge J, Gordon, Brian A., Sánchez-Valle, Raquel, (DIAN), The Dominantly Inherited Alzheimer Network, Daniels, Alisha , Courtney, Laura, Ziegemeier, Angela, Skrbec, Karina, Hellm, Cortaiga, Martin, Mariana , Ziegemeier, Ellen , Bartzel, Jamie, Xiong, Chengie , Xu, Xiong, Lu, Ruijin, Li, Yan , Nie, Yuzheng , Gremminger, Emily, Perrin, Richard J. , Franklin, Erin , Ibanez, Laura, Jerome, Gina, Stauber, Jennifer, Baker, Bryce, Minton, Matthew, Cruchaga, Carlos C, Goate, Alison M, Renton, Alan E, Picarello, Danielle M. , Benzinger, Tammie L S, Hornbeck, Russ C. , Chen, Allison, Chen, Charles D., Flores, Shaney, Joseph-Mathurin, Nelly, Jackson, Kelley, Keefe, Sarah , Koudelis, Deborah, Massoumzadeh, Parinaz , Nicklaus, Joyce , Pulizos, Christine, Wang, Qing, Sabaredzovic, Edita, Scott, Jalen , Simmons, Ashlee, Rizzo, Jacqueline, Vlassenko, Andrei G. , Wang, Yong, Hassenstab, Jason, Smith, Jennifer, Stout, Sarah, Marsh, Jacob, Morris, John C, Barthélemy, Nicolas R. , Xu, Jinbin , Ikonomović, Snežana, Graff-Radford, Neill R, Farlow, Martin R. , Chhatwal, Jasmeer P. , Maa, Courtney, Ishiguro, Takanobu , Ishii, Kenji, Senda, Michio, Salloway, Stephen , Bechara, Jacob A, Martins, Ralph, Fox, Nick C, Ryan, Natalie S. , Laske, Christoph , Timofejavaite, Reda, Kuder-Buletta, Elke, Graber-Sultan, Susanne, Obermueller, Ulrike, Xiong, Chengjie , Rödenbeck, Yvonne, Vӧglein, Jonathan, Méndez, Patricio Chrem, Vazquez, Silvia, Leon, Yudy Milena, Ramirez, Laura, Baena, Ana , Bocanegra, Yamile , Levey, Allan, Johnson, Erik C B, Seyfried, Nicholas T. , Ringman, John M. , Fagan, Anne M. , Mori, Hiroshi, Lopera, Francisco , Goate, Alison , Hassenstab, Jason , Borrego‐Écija, Sergi , Pérez‐Millan, Agnès , Ikeuchi, T , Vöglein, Jonathan , Roh, Jee Hoon , Vitali, Paolo , Gordon, Brian A , Bateman, Randall J , Sánchez-Valle, Raquel , Day, Gregory S , Xiong, Chengjie , Hassenstab, Jason , Borrego-Écija, Sergi , Goate, Alison M , Bosch, Beatríz , Antonell, Anna, Fernández‐Villullas, Guadalupe , Esteller, Diana , Tort‐Merino, Adrià , Balasa, Mircea , Lladó, Albert , Aguillon, David , Ikeuchi, Takeshi , Jucker, Mathias , Kasuga, Kensaku , Vöglein, Jonathan , Llibre‐Guerra, Jorge J. , Gordon, Brian A. , McDade, Eric , Bateman, Randall J. , Sánchez‐Valle, Raquel , Supnet, Charlene , Lu, Ruijin, Wang, Guoqiao , Ibanez, Laura , Cruchaga, Carlos , Fulton‐Howard, Brian , Banks, Jessica N , Flores, Shaney , Goyal, Manu S. , Hobbs, Diana A. , Joseph‐Mathurin, Nelly , McCullough, Austin , McKay, Nicole S. , Wang, Yong , Smith, Jennifer, Stout, Sarah H., Aschenbrenner, Andrew J. , Karch, Celeste M. , Marsh, Jacob A. , Holtzman, David M. , Berman, Sarah , Graff‐Radford, Neill R. , Senda, Michio , Niimi, Yoshiki , Schofield, Peter R. , Brooks, William S. , Bechara, Jacob , Cash, David M. , Laske, Christoph , Fougère, Christian la , Reischl, Gerald , Lee, Jae Hong , Allegri, Ricardo , Surace, Ezequiel , Vazquez, Silvia, Ramírez, Laura, Serna, Laura, Johnson, Erik C. B. , Masters, Colin L. , Noble, James M. , Lopera, Francisco Javier
Brain Communications | December 18, 2025 | Volume: 8 | Issue: 1 | Pages: No page available
Abstract The cortical asymmetry index evaluates the cortical thickness asymmetry between hemispheres. We investigated cortical asymmetry index in asymptomatic and symptomatic mutation carriers of autosomal dominant Alzheimer’s disease to explore the brain asymmetry within the Alzheimer’s disease continuum. Sixty baseline T1-weighted MRI scans were obtained from the Clinic Barcelona cohort. Baseline and longitudinal MRI data from 564 participants within the dominantly inherited Alzheimer network observational study were used as an independent, confirmatory cohort. Cerebrospinal fluid and plasma neurofilament light chain levels were included when available. Cortical thickness was calculated using Freesurfer and cortical asymmetry index was calculated via an open-source pipeline. Cross-sectional analyses examined cortical asymmetry index differences based on clinical classification and APOE ε4 status, adjusting for age, sex and estimated years from onset, while correlations were assessed with age, estimated years from onset, mini-mental state examination scores, and neurofilament light. Longitudinal cortical asymmetry index evolution was modelled using generalized additive models in the dominantly inherited Alzheimer network observational study cohort, incorporating age, sex, and the interaction between group and estimated years from onset. The cortical asymmetry index successfully distinguished asymptomatic mutation carrier and symptomatic mutation carriers from healthy controls in the Clinic Barcelona cohort and symptomatic mutation carriers from controls in dominantly inherited Alzheimer network observational study. Higher cortical asymmetry index in mutation carriers (asymptomatic mutation carrier and symptomatic mutation carriers combined) and in symptomatic mutation carriers were associated with higher plasma neurofilament light levels, a closer proximity to symptom onset, and lower mini-mental state examination in the Clinic Barcelona cohort. In the dominantly inherited Alzheimer network observational study cohort, mutation carriers exhibited increased cortical asymmetry index compared to controls and correlated with elevated neurofilament light (plasma and Cerebrospinal fluid), lower mini-mental state examination, and a closer proximity to symptom onset. APOE3/3 carriers showed greater asymmetry than other APOE genotypes and significant cortical asymmetry index differences between asymptomatic mutation carrier and symptomatic mutation carriers. Longitudinally, cortical asymmetry index increased over time significantly in symptomatic mutation carriers. These findings underscore brain asymmetry as a potential biomarker for early Alzheimer’s disease progression in autosomal dominant Alzheimer’s disease, with implications for detection and monitoring tracking disease-related neuroanatomical changes.
Cross‐Sectional FDG in Down Syndrome and Autosomal Dominant Alzheimer's Disease
Abdelmoity, Omar , Wisch, Julie K. , Kennedy, James T. , Vlassenko, Andrei G. , Handen, Benjamin L. , Head, Elizabeth , Lai, Florence , Rosas, H. Diana , Hartley, Sigan L. , Tudorascu, Dana , Keefe, Sarah , Ikeuchi, Takeshi, Morris, John C., Roh, Jee Hoon , Day, Gregory S. , Xiong, Chengjie , Head, Elizabeth , Lao, Patrick , Keefe, Sarah , Roh, Jee Hoon , Day, Gregory S , Gordon, Brian A , Xiong, Chengjie , Wisch, Julie K , Goyal, Manu S. , Flores, Shaney , Keator, David B. , Rafii, Michael S. , Zaman, Shahid H. , Brickman, Adam M. , Lee, Joseph H. , Allegri, Ricardo , Fougère, Christian la , Llibre‐Guerra, Jorge J. , Ikeuchi, Takeshi , Morris, John C. , Schofield, Peter R. , Gordon, Brian A. , Benzinger, Tammie L.S. , Ances, Beau M.
Annals of Neurology | September 22, 2025 | Volume: 98 | Issue: 6 | Pages: 1237-1248
Objectives Directly compare the brain glucose patterns seen with [F‐18] fluorodeoxyglucose (FDG) positron emission tomography (PET) between 2 genetically determined forms of Alzheimer's disease: Down syndrome (DS) and autosomal dominant Alzheimer's disease (ADAD). Methods Cross‐sectional analyses of FDG were performed in individuals with DS (n = 76) from the Alzheimer Biomarker Consortium‐Down Syndrome (ABC‐DS), ADAD (n = 297), and neurotypical familial controls (n = 188) from the Dominantly Inherited Alzheimer Network (DIAN). Within‐group linear regression models and generalized additive models were performed for select regional FDG uptake measures (isthmus cingulate and inferior parietal, precuneus, middle temporal gyrus, and precentral gyrus). Age, sex, apolipoprotein (APOE) ε4 carrier status, and cortical amyloid burden were included within these analyses. Results Even 20 years before expected onset of clinical symptoms, FDG uptake was lower for DS compared to neurotypical familial controls ( p < 0.01). ADAD baseline FDG was similar to neurotypical familial controls until 7 years before expected symptom onset. Both symptomatic individuals with DS and ADAD had lower FDG compared to neurotypical familial controls ( p < 0.01). A higher amyloid burden was associated with lower FDG for both genetic forms, with similar rates of decline in FDG uptake for DS and ADAD who were amyloid positive. Interpretation Brain glucose metabolism is substantially lower for people with DS, even in individuals who are cognitively stable. The patterns of FDG decline are distinct in these 2 genetically determined forms of AD. The diagnostic utility of FDG‐PET is specific to the genetic form of AD. ANN NEUROL 2025;98:1237–1248