Autosomal dominant and sporadic late onset Alzheimer's disease share a common in vivo pathophysiology
Year: 2022
Type: article
Abstract: The extent to which the pathophysiology of autosomal dominant Alzheimer's disease corresponds to the pathophysiology of 'sporadic' late onset Alzheimer's disease is unknown, thus limiting the extrapolation of study findings and clinical trial results in autosomal dominant Alzheimer's disease to late onset Alzheimer's disease. We compared brain MRI and amyloid PET data, as well as CSF concentrations of amyloid-β42, amyloid-β40, tau and tau phosphorylated at position 181, in 292 carriers of pathogenic variants for Alzheimer's disease from the Dominantly Inherited Alzheimer Network, with corresponding data from 559 participants from the Alzheimer's Disease Neuroimaging Initiative. Imaging data and CSF samples were reprocessed as appropriate to guarantee uniform pipelines and assays. Data analyses yielded rates of change before and after symptomatic onset of Alzheimer's disease, allowing the alignment of the ∼30-year age difference between the cohorts on a clinically meaningful anchor point, namely the participant age at symptomatic onset. Biomarker profiles were similar for both autosomal dominant Alzheimer's disease and late onset Alzheimer's disease. Both groups demonstrated accelerated rates of decline in cognitive performance and in regional brain volume loss after symptomatic onset. Although amyloid burden accumulation as determined by PET was greater after symptomatic onset in autosomal dominant Alzheimer's disease than in late onset Alzheimer's disease participants, CSF assays of amyloid-β42, amyloid-β40, tau and p-tau181 were largely overlapping in both groups. Rates of change in cognitive performance and hippocampal volume loss after symptomatic onset were more aggressive for autosomal dominant Alzheimer's disease participants. These findings suggest a similar pathophysiology of autosomal dominant Alzheimer's disease and late onset Alzheimer's disease, supporting a shared pathobiological construct.
Source: Brain
Authors: John C Morris, Michael Weiner, Chengjie Xiong, Laurel Beckett, Dean Coble, Naomi Saito, Paul S Aisen, Ricardo Allegri, Tammie L S Benzinger, Sarah B Berman, Nigel J Cairns, Maria C Carrillo, Helena C Chui, Jasmeer P Chhatwal, Carlos Cruchaga, Anne M Fagan, Martin Farlow, Nick C Fox, Bernardino Ghetti, Alison M Goate, Brian A Gordon, Neill Graff-Radford, Gregory S Day, Jason Hassenstab, Takeshi Ikeuchi, Clifford R Jack, William J Jagust, Mathias Jucker, Johannes Levin, Parinaz Massoumzadeh, Colin L Masters, Ralph Martins, Eric McDade, Hiroshi Mori, James M Noble, Ronald C Petersen, John M Ringman, Stephen Salloway, Andrew J Saykin, Peter R Schofield, Leslie M Shaw, Arthur W Toga, John Q Trojanowski, Jonathan Vöglein, Stacie Weninger, Randall J Bateman, Virginia D Buckles
Institutions: Washington University in St. Louis, University of California, San Francisco, University of California, Davis, University of Southern California, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia, University of Pittsburgh, University of Exeter, Alzheimer's Association, Massachusetts General Hospital, Indiana University School of Medicine, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, University College London, Indiana University Indianapolis, Icahn School of Medicine at Mount Sinai, Mayo Clinic in Florida, Brain Research Institute, Niigata University, Niigata University, Mayo Clinic, University of California, Berkeley, German Center for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Munich Cluster for Systems Neurology, Ludwig-Maximilians-Universität München, The University of Melbourne, Florey Institute of Neuroscience and Mental Health, Edith Cowan University, Osaka City University, Columbia University Irving Medical Center, Brown University, Butler Hospital, Indiana University – Purdue University Indianapolis, UNSW Sydney, Neuroscience Research Australia, University of Pennsylvania
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
Funders: U.S. Department of Defense, Alzheimer's Association, Bristol-Myers Squibb, Pfizer, Biogen, University of Southern California, Meso Scale Diagnostics, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Novartis Pharmaceuticals Corporation, Japan Agency for Medical Research and Development, Northern California Institute for Research and Education, National Institute for Health and Care Research, Eisai, Deutsches Zentrum für Neurodegenerative Erkrankungen, University College London Hospitals NHS Foundation Trust, Servier, H. Lundbeck A/S, IXICO, Fleni, Dementias Platform UK, National Institutes of Health, Genentech, Canadian Institutes of Health Research, Medical Research Council, National Institute on Aging, Johnson and Johnson Pharmaceutical Research and Development, Janssen Alzheimer Immunotherapy Research And Development
Awards: G104586243, UK Dementias Platform, G2992001090, PURCHASE OF A SIEMENS NEXT GENERATION PET/CT, G563411468, Alzheimer's Disease Neuroimaging Initiative, Dominantly Inherited Alzheimer Network, G7104243095, Healthy Aging and Senile Dementia, G7724524774, Dominantly Inherited Alzheimer Network, Alzheimer's Disease Research Center, Alzheimer's Disease Neuroimaging Initiative (ADNI4), Alzheimer's Disease Research Centers, Penn Alzheimer's Disease Research Center (ADRC), Antecedent Biomarkers for Alzheimer Disease: The Adult Children Study, Neuroimaging Markers of Emerging Dysfunction In Preclinical Alzheimer Disease
OpenAlex ID: W4280526065