Uncovering atrophy progression pattern and mechanisms in individuals at risk of Alzheimer's disease

• DOI: 10.1093/braincomms/fcaf099
• Publication Date: 2025-03-05T01:42:56Z
• Authors: Christina Tremblay; Shady Rahayel; Alexandre Pastor-...; Frédéric St-Onge; Andrew Vo; François Rheault; Véronique Daneault; Filip Morys; Natasha Rajah; Sylvia Villeneuve; Alain Dagher; ; John Breitner; Sylvain Baillet; Pierre Bellec; Véronique Bohbot; Mallar Chakravarty; D Louis Collins; Pierre Etienne; Alan Evans; Serge Gauthier; Rick Hoge; Yasser Ituria-Medina; Gerhard Multhaup; Lisa-Marie Münter; Vasavan Nair; Judes Poirier; Natasha Rajah; Pedro Rosa-Neto; Jean-Paul Soucy; Etienne Vachon-Pr...; Sylvia Villeneuve; Philippe Amouyel; Melissa Appleby; Nicholas Ashton; Gülebru Ayranci; Christophe Bedetti; Jason Brandt; Ann Brinkmalm Wes...; Claudio Cuello; Mahsa Dadar; Leslie-Ann Daoust; Samir Das; Marina Dauar-Tede...; Louis De Beaumont; Doris Dea; Maxime Descoteaux; Marianne Dufour; Sarah Farzin; Fabiola Ferdinand; Vladimir Fonov; David Fontaine; Guylaine Gagné; Julie Gonneaud; Justin Kat; Christina Kazazian; Anne Labonté; Marie-Elyse Lafai...; Marc Lalancette; Jean-Charles Lambert; Jeannie-Marie Leo...; Claude Lepage; Cécile Madjar; David Maillet; Jean-Robert Maltais; Sulantha Mathotaa...; Ginette Mayrand; Diane Michaud; Thomas Montine; John Morris; Véronique Pagé; Tharick Pascoal; Sandra Peillieux; Mirela Petkova; Pierre Rioux; Mark Sager; Eunice Farah Sain...; Mélissa Savard; Reisa Sperling; Shirin Tabrizi; Pierre Tariot; Eduard Teigner; Ronald Thomas; Paule-Joanne Tous...; Miranda Tuwaig; Vinod Venugopalan; Sander Verfaillie; Jacob Vogel; Karen Wan; Seqian Wang; Elsa Yu; ; R C Petersen; P S Aisen; L A Beckett; M C Donohue; A C Gamst; D J Harvey; C R Jack; W J Jagust; L M Shaw; A W Toga; J Q Trojanowski; M W Weiner
• Keywords: Amyloid beta; Amyloid (mycology)

Abstract Alzheimer's disease is associated with pre-symptomatic changes in brain morphometry and accumulation of abnormal tau amyloid-beta pathology. Studying the development prior to symptoms onset may lead early diagnostic biomarkers a better understanding pathophysiology. pathology thought arise from combination protein spreading via neural connections, but how these processes influence atrophy progression phases remains unclear. Individuals family history (FHAD) have an elevated risk disease, providing opportunity study phase. Here, we used structural MRI three databases (Alzheimer's Disease Neuroimaging Initiative, Pre-symptomatic Evaluation Experimental or Novel Treatments for Alzheimer Montreal Adult Lifespan Study) map FHAD assess constraining effects connectivity on progression. Cross-sectional longitudinal data up 4 years were perform analysis compared controls. PET radiotracers also quantify distribution isoforms at baseline. We first derived cortical maps using deformation-based 153 FHAD, 156 116 controls similar age, education sex next examined spatial relationship between patterns aggregates plaques deposition, neurotransmitter receptor transporter distributions. Our results show that there notably cingulate, temporal parietal cortices, more widespread severe disease. Both tended accumulate regions structurally connected The pattern its aligned existing FHAD. In our findings suggest propagation occurred earlier, previously intact connectome. Moreover, was found serotonin current demonstrates showing present specific cellular characteristics, uncovering some mechanisms involved pre-clinical clinical neurodegeneration.