Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia
Year: 2022
Type: article
Study design: Case Report
Abstract: We describe in vivo follow-up PET imaging and postmortem findings from an autosomal dominant Alzheimer's disease (ADAD) PSEN1 E280A carrier who was also homozygous for the APOE3 Christchurch (APOE3ch) variant and was protected against Alzheimer's symptoms for almost three decades beyond the expected age of onset. We identified a distinct anatomical pattern of tau pathology with atypical accumulation in vivo and unusual postmortem regional distribution characterized by sparing in the frontal cortex and severe pathology in the occipital cortex. The frontal cortex and the hippocampus, less affected than the occipital cortex by tau pathology, contained Related Orphan Receptor B (RORB) positive neurons, homeostatic astrocytes and higher APOE expression. The occipital cortex, the only cortical region showing cerebral amyloid angiopathy (CAA), exhibited a distinctive chronic inflammatory microglial profile and lower APOE expression. Thus, the Christchurch variant may impact the distribution of tau pathology, modulate age at onset, severity, progression, and clinical presentation of ADAD, suggesting possible therapeutic strategies.
Source: Acta Neuropathologica
Authors: Diego Sepulveda-Falla, Justin S. Sanchez, Maria Camila Almeida, Daniela Boassa, Juliana Acosta-Uribe, Clara Vila-Castelar, Liliana Ramirez-Gomez, Ana Baena, David Aguillon, Nelson David Villalba-Moreno, Jessica Lisa Littau, Andres Villegas, Thomas G. Beach, Charles L. White, Mark Ellisman, Susanne Krasemann, Markus Glatzel, Keith A. Johnson, Reisa A. Sperling, Eric M. Reiman, Joseph F. Arboleda-Velasquez, Kenneth S. Kosik, Francisco Lopera, Yakeel T. Quiroz
Institutions: University Medical Center Hamburg-Eppendorf, Harvard University, Massachusetts General Hospital, University of California, Santa Barbara, Universidade Federal do ABC, University of California San Diego, Universidad de Antioquia, Banner Sun Health Research Institute, The University of Texas Southwestern Medical Center, Banner Alzheimer’s Institute, Massachusetts Eye and Ear Infirmary
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,790
Funders: Alzheimer's Association, Massachusetts General Hospital, Deutsche Forschungsgemeinschaft, Fundação de Amparo à Pesquisa do Estado de São Paulo, Bundesministerium für Bildung und Forschung, Universidad de Antioquia, Werner Otto Stiftung, Universitätsklinikum Hamburg-Eppendorf, National Institute on Aging, National Institute of Neurological Disorders and Stroke
Awards: G1022338080, Identifizierung von Hirnzelltypspezifischen Genregulationsnetzwerken bei Patienten mit familiärer AlzheimerKrankheit PSEN1 E280A, Charting vascular contributions to white matter disease in familial Alzheimer's disease and CADASIL, The complex interaction between Alzheimer drivers and aging, 3D Reconstruction and Analysis of Alzheimer's Patient Biopsy Samples to Map and Quantify Hallmarks of Pathogenesis and Vulnerability, Exploring the Role of Aging in Cerebral Ischemic Small Vessel Disease Using Notch3 Mutant Mice, Arizona Alzheimer's Disease Core Center, Relationship between tau pathology and cognitive impairment in autosomal dominant Alzheimer's disease, Arizona Alzheimer's Disease Research Center, National Center for Microscopy and Imaging Research: A BRAIN Technology Integration and Dissemination Resource, Massachusetts Alzheimer's Disease Research Center (MADRC)
OpenAlex ID: W4285589271