Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

Autor: Arboleda-Velasquez JF; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. joseph_arboleda@meei.harvard.edu., Lopera F; Grupo de Neurociencias de Antioquia de la Universidad de Antioquia, Medellin, Colombia., O'Hare M; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology, Harvard Medical School, Boston, MA, USA., Delgado-Tirado S; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology, Harvard Medical School, Boston, MA, USA., Marino C; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology, Harvard Medical School, Boston, MA, USA., Chmielewska N; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.; Boston College, Boston, MA, USA., Saez-Torres KL; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology, Harvard Medical School, Boston, MA, USA., Amarnani D; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology, Harvard Medical School, Boston, MA, USA., Schultz AP; Massachusetts General Hospital and Department of Neurology, Harvard Medical School, Boston, MA, USA., Sperling RA; Massachusetts General Hospital and Department of Neurology, Harvard Medical School, Boston, MA, USA.; Brigham and Women's Hospital and the Department of Neurology, Harvard Medical School, Boston, MA, USA., Leyton-Cifuentes D; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.; Universidad Escuela de Ingenieria de Antioquia-EIA, Medellin, Colombia., Chen K; The Banner Alzheimer's Institute, Phoenix, AZ, USA.; University of Arizona, Tucson, AZ, USA.; Arizona State University, Tempe, AZ, USA., Baena A; Grupo de Neurociencias de Antioquia de la Universidad de Antioquia, Medellin, Colombia., Aguillon D; Grupo de Neurociencias de Antioquia de la Universidad de Antioquia, Medellin, Colombia., Rios-Romenets S; Grupo de Neurociencias de Antioquia de la Universidad de Antioquia, Medellin, Colombia., Giraldo M; Grupo de Neurociencias de Antioquia de la Universidad de Antioquia, Medellin, Colombia., Guzmán-Vélez E; Massachusetts General Hospital and the Department of Psychiatry, Harvard Medical School, Boston, MA, USA., Norton DJ; Massachusetts General Hospital and the Department of Psychiatry, Harvard Medical School, Boston, MA, USA.; Department of Psychology, Gordon College, Wenham, MA, USA., Pardilla-Delgado E; Massachusetts General Hospital and the Department of Psychiatry, Harvard Medical School, Boston, MA, USA., Artola A; Massachusetts General Hospital and the Department of Psychiatry, Harvard Medical School, Boston, MA, USA., Sanchez JS; Massachusetts General Hospital and Department of Neurology, Harvard Medical School, Boston, MA, USA., Acosta-Uribe J; Grupo de Neurociencias de Antioquia de la Universidad de Antioquia, Medellin, Colombia.; Neuroscience Research Institute, Department of Molecular Cellular Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA., Lalli M; Neuroscience Research Institute, Department of Molecular Cellular Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA., Kosik KS; Neuroscience Research Institute, Department of Molecular Cellular Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA., Huentelman MJ; Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, USA., Zetterberg H; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.; UK Dementia Research Institute at UCL, London, UK., Blennow K; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden., Reiman RA; Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, USA., Luo J; The Banner Alzheimer's Institute, Phoenix, AZ, USA., Chen Y; The Banner Alzheimer's Institute, Phoenix, AZ, USA., Thiyyagura P; The Banner Alzheimer's Institute, Phoenix, AZ, USA., Su Y; The Banner Alzheimer's Institute, Phoenix, AZ, USA., Jun GR; Department of Medicine, Boston University School of Medicine, Boston, MA, USA., Naymik M; Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, USA., Gai X; Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.; Department of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA., Bootwalla M; Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA., Ji J; Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.; Department of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA., Shen L; Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA., Miller JB; Mass Eye and Ear and Department of Ophthalmology, Harvard Medical School, Boston, MA, USA., Kim LA; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology, Harvard Medical School, Boston, MA, USA., Tariot PN; The Banner Alzheimer's Institute, Phoenix, AZ, USA.; University of Arizona, Tucson, AZ, USA., Johnson KA; Massachusetts General Hospital and Department of Neurology, Harvard Medical School, Boston, MA, USA.; Brigham and Women's Hospital and the Department of Neurology, Harvard Medical School, Boston, MA, USA.; Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA, USA., Reiman EM; The Banner Alzheimer's Institute, Phoenix, AZ, USA. eric.reiman@bannerhealth.com.; University of Arizona, Tucson, AZ, USA. eric.reiman@bannerhealth.com.; Arizona State University, Tempe, AZ, USA. eric.reiman@bannerhealth.com.; Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, USA. eric.reiman@bannerhealth.com., Quiroz YT; Grupo de Neurociencias de Antioquia de la Universidad de Antioquia, Medellin, Colombia. yquiroz@mgh.harvard.edu.; Massachusetts General Hospital and Department of Neurology, Harvard Medical School, Boston, MA, USA. yquiroz@mgh.harvard.edu.; Massachusetts General Hospital and the Department of Psychiatry, Harvard Medical School, Boston, MA, USA. yquiroz@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2019 Nov; Vol. 25 (11), pp. 1680-1683. Date of Electronic Publication: 2019 Nov 04.
DOI: 10.1038/s41591-019-0611-3
Abstrakt: We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.
Databáze: MEDLINE