Citations 2
Associations of lifestyle factors with amyloid pathology in persons without dementia
Oomens, Julie Elisabeth , Vos, Stephanie J. B. , Maserejian, Nancy N., Didic, Mira , Engelborghs, Sebastiaan , Fladby, Tormod, Fröhlich, Lutz, Gill, Kiran Dip, Grimmer, Timo, Itoh, Yoshiaki , Landau, Susan, Lleó, Alberto, Meyer, Philipp T. , Pardini, Matteo , Rami, Lorena , Reiman, Eric M. , Rinne, Juha O. , Sánchez‐Juan, Pascual, Scarmeas, Nikolaos , Villeneuve, Sylvia , Waldemar, Gunhild , Alcolea, Daniel, Altomare, Daniele , Baldeiras, Inês , Blennow, Kaj , Cerman, Jiří , Chipi, Elena , Day, Gregory S. , Förster, Stefan , Frings, Lars , Guedj, Éric , Habeck, Christian , Hausner, Lucrezia , Jiménez‐Bonilla, J., Juaristi, Arantxa, Kern, Silke , Kirsebom, Bjørn‐Eivind , Legdeur, Nienke , Xiong, Chengjie , Maier, W., Marquié, Marta, Minatani, Shinobu, Prabhakar, Sudesh, Ramakers, Inez H.G.B. , Rodríguez‐Rodríguez, Eloy , Ruiz, Agustín, Rüther, E., Sakhardande, Jayant, Selnes, Per, Spiru, Luiza , Vermunt, Lisa , Wallin, Åsa K., Zettergren, Anna , (ADNI), for the Alzheimer's Disease Neuroimaging Initiative, group, A4 Study, (DIAN), Dominantly Inherited Alzheimer Network, (KBASE), Japan Alzheimer's Disease Neuroimaging Initiative (J-ADNI), Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, Ossenkoppele, Rik, Verhey, Frans RJ, Visser, Pieter Jelle, Jansen, Willemijn J, Marquié, Marta , Selnes, Per , Day, Gregory S , Xiong, Chengjie , Oomens, Julie E , Boada, Merçé , Fladby, Tormod , Flier, Wiesje M. van der , Frisoni, Giovanni B. , Fröhlich, Lutz, Grimmer, Timo , Hort, Jakub , Iwatsubo, Takeshi , Klimkowicz‐Mrowiec, Aleksandra , Lee, Dong Young , Lleó, Alberto , Martínez‐Lage, Pablo , Mendonça, Alexandre de , Parchi, Piero , Parnetti, Lucilla , Popp, Julius , Rodrigue, Karen M. , Santana, Isabel , Scheltens, Philip , Skoog, Ingmar , Sperling, Reisa Anne , Stern, Yaakov , Wiltfang, Jens , Zetterberg, Henrik , Alcolea, Daniel , Allegri, Ricardo , Bateman, Randall J. , Baiardi, Simone , Braber, Anouk den , Buchem, Mark A. van , Byun, Min Soo , Chen, Kewei , Drzezga, Alexander E. , Ekblad, Laura L. , Fortea, Juan , Freund‐Levi, Yvonne , Handels, Ron , Hellwig, Sabine , Kandimalla, Ramesh , Kornhuber, Johannes , Morbelli, Silvia , Mroczko, Barbara , Ntanasi, Eva , Oliveira, Catarina Resende , Orellana, Adelina , Peters, Oliver , Ruiz, Agustı́n , Silva, Dina , Soininen, Hilkka S. , Takeda, Akitoshi , Teunissen, Charlotte E. , Tijms, Betty M. , Wiels, Wietse A. , Yannakoulia, Mary , Yi, Dahyun , (ADNI), for the Alzheimer's Disease Neuroimaging Initiative, group, A4 Study, (DIAN), Dominantly Inherited Alzheimer Network, (KBASE), Japan Alzheimer's Disease Neuroimaging Initiative (J-ADNI), Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, Ossenkoppele, Rik, Verhey, Frans R.J. , Visser, Pieter Jelle , Jansen, Willemijn J.
Journal of Alzheimer’s Disease | November 14, 2025 | Volume: 108 | Issue: 3 | Pages: 1043-1059
Background The association between lifestyle factors and Alzheimer's disease (AD) pathophysiology remains incompletely understood. Objective The aim of this study was to assess the association of alcohol consumption, smoking behavior, sleep quality and physical, cognitive, and social activity with cerebral amyloid pathology. Methods For this cross-sectional study, we selected participants from the Amyloid Biomarker Study data pooling initiative. We used generalized estimating equations to assess associations of dichotomized lifestyle measures with amyloid pathology. Results We included 9171 participants with normal cognition (NC) and 2555 participants with mild cognitive impairment (MCI) from the Amyloid Biomarker Study. Of participants with NC, 58% were women, 34% were APOE ε4 carrier, and 27% had amyloid pathology. Of participants with MCI, 48% were women, 47% were APOE ε4 carrier, and 57% had amyloid pathology. In NC, cognitively active participants were less likely to have amyloid pathology (OR = 0.77, 95%CI 0.66–0.89, p < 0.001). In MCI, participants who had ever smoked or had sleep problems were less likely to have amyloid pathology (OR = 0.85, 95%CI 0.73–0.99, p = 0.029; OR = 0.62, 95%CI 0.45–0.86, p = 0.004). Conclusions In NC, cognitive activity was associated with a lower frequency of amyloid pathology. In MCI, favorable lifestyle behaviors were not associated with a lower frequency of amyloid pathology. The results of the current study contribute to the broader evidence base on lifestyle and AD by further characterizing the role of lifestyle behaviors in AD pathology across different clinical stages.
Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Guen, Yann Le , Luo, Guo , Damotte, Vincent , Jansen, Iris E. , Nicolas, Aude , Rojas, Itziar de, Bellenguez, Céline , Lian, Michelle Mulan , Parveen, Kayenat, Morizono, Takashi, Park, Hyeonseul, Grenier‐Boley, Benjamin , Naito, Tatsuhiko , Talyansky, Seth D., Yogeshwar, Selina , Sempere, Vicente Peris, Satake, Wataru , Álvarez, Victoria , Arosio, Beatrice , Boland, Anne , Daniele, Antonio , Darling, D.H., Dichgans, Martin , Dufouil, Carole , Düzel, Emrah , García‐Ribas, Guillermo, García‐Alberca, José María , García-González, Pablo, Giedraitis, Vilmantas , Graff, Caroline , Grünblatt, Edna , Hausner, Lucrezia , Jung, Yoo Jin , Deckert, Jürgen, Kern, Silke , Kuulasmaa, Teemu , Lee, Kun Ho , Lin, Ling , Masullo, Carlo , Mehrabian, Shima , Mendonça, Alexandre de , Boada, Merçé , Mir, Pablo , Moreno, Fermín , Nicolas, Gaël , Niida, Shumpei , Nordestgaard, Børge G. , Papenberg, Goran, Papma, Janne M., Pástor, Pau , Peters, Oliver , Popp, Julius , Molina‐Porcel, Laura , Puerta, Raquel , Pérez‐Tur, Jordi , Ramakers, Inez H.G.B. , Real, Luís Miguel , Riedel‐Heller, Steffi G. , Rodríguez‐Rodríguez, Eloy , Ross, Owen A. , Scarmeas, Nikolaos , Schneider, Anja , Solfrizzi, Vincenzo , Spalletta, Gianfranco , Tan, Eng‐King , Tegos, Thomas, Thomassen, Jesper Qvist , Tremolizzo, Lucio , Verhey, Frans, EADB, group, GR@ACE study, DemGene, EADI, GERAD, Blennow, Kaj , He, Zihuai , Jessen, Frank , Kehoe, Patrick G. , Duin, Cornelia van, Sánchez‐Juan, Pascual , Zettergren, Anna , Okada, Yukinori , Rossi, Giacomina, Gim, Jungsoo , Sims, Rebecca, Ramı́rez, Alfredo , Lambert, Jean‐Charles , Greicius, Michael D. , Mignot, Emmanuel , Moreno–Grau, Sonia , Rojas, Itziar de, Prokic, Ivana, Aarsland, Dag, García‐González, Pablo , Abdelnour, Carla , Armstrong, Nicola J. , Anthoula, Tsolaki, Archetti, Silvana, Pastor, Alfonso Arias, Athanasiu, Lavinia, Bailly, Henri, Banaj, Nerisa , Baquero, Miquel , Pastor, Ana Belén , Besse, Céline , Bizarro, Alessandra, Blesa, Rafael , Bossù, Paola , Brusco, 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Proceedings of the National Academy of Sciences | August 29, 2023 | Volume: 120 | Issue: 36 | Pages: No page available
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.