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Resilience to autosomal dominant Alzheimer's disease in a Reelin-COLBOS heterozygous man.
Lopera, Francisco; Marino, Claudia; Chandrahas, Anita S; O'Hare, Michael; Villalba-Moreno, Nelson David; Aguillon, David; Baena, Ana; Sanchez, Justin S; Vila-Castelar, Clara; Ramirez Gomez, Liliana; Chmielewska, Natalia; Oliveira, Gabriel M; Littau, Jessica Lisa; Hartmann, Kristin; Park, Kyungeun; Krasemann, Susanne; Glatzel, Markus; Schoemaker, Dorothee; Gonzalez-Buendia, Lucia; Delgado-Tirado, Santiago; Arevalo-Alquichire, Said; Saez-Torres, Kahira L; Amarnani, Dhanesh; Kim, Leo A; Mazzarino, Randall C; Gordon, Harper; Bocanegra, Yamile; Villegas, Andres; Gai, Xiaowu; Bootwalla, Moiz; Ji, Jianling; Shen, Lishuang; Kosik, Kenneth S; Su, Yi; Chen, Yinghua; Schultz, Aaron; Sperling, Reisa A; Johnson, Keith; Reiman, Eric M; Sepulveda-Falla, Diego; Arboleda-Velasquez, Joseph F; Quiroz, Yakeel T.
Affiliation
  • Lopera F; Neuroscience Group of Antioquia, Medicine School, University of Antioquia, Medellín, Colombia.
  • Marino C; Medicine School, University of Antioquia, Medellín, Colombia.
  • Chandrahas AS; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
  • O'Hare M; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
  • Villalba-Moreno ND; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
  • Aguillon D; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Baena A; Neuroscience Group of Antioquia, Medicine School, University of Antioquia, Medellín, Colombia.
  • Sanchez JS; Medicine School, University of Antioquia, Medellín, Colombia.
  • Vila-Castelar C; Neuroscience Group of Antioquia, Medicine School, University of Antioquia, Medellín, Colombia.
  • Ramirez Gomez L; Department of Neurology at Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
  • Chmielewska N; Department of Psychiatry at Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
  • Oliveira GM; Department of Neurology at Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
  • Littau JL; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
  • Hartmann K; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
  • Park K; Department of Psychiatry at Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
  • Krasemann S; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Glatzel M; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Schoemaker D; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Gonzalez-Buendia L; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Delgado-Tirado S; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Arevalo-Alquichire S; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
  • Saez-Torres KL; Department of Psychiatry at Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
  • Amarnani D; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
  • Kim LA; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
  • Mazzarino RC; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
  • Gordon H; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
  • Bocanegra Y; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
  • Villegas A; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
  • Gai X; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
  • Bootwalla M; Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
  • Ji J; Neuroscience Group of Antioquia, Medicine School, University of Antioquia, Medellín, Colombia.
  • Shen L; Neuroscience Group of Antioquia, Medicine School, University of Antioquia, Medellín, Colombia.
  • Kosik KS; Medicine School, University of Antioquia, Medellín, Colombia.
  • Su Y; Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Chen Y; Department of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
  • Schultz A; Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Sperling RA; Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Johnson K; Department of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
  • Reiman EM; Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Sepulveda-Falla D; Neuroscience Research Institute, Department of Molecular Cellular Developmental Biology, University of California, Santa Barbara, CA, USA.
  • Arboleda-Velasquez JF; The Banner Alzheimer's Institute, Phoenix, AZ, USA.
  • Quiroz YT; The Banner Alzheimer's Institute, Phoenix, AZ, USA.
Nat Med ; 29(5): 1243-1252, 2023 05.
Article in En | MEDLINE | ID: mdl-37188781
ABSTRACT
We characterized the world's second case with ascertained extreme resilience to autosomal dominant Alzheimer's disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation. Like the APOECh carrier, he had extremely elevated amyloid plaque burden and limited entorhinal Tau tangle burden. He did not carry the APOECh variant but was heterozygous for a rare variant in RELN (H3447R, termed COLBOS after the Colombia-Boston biomarker research study), a ligand that like apolipoprotein E binds to the VLDLr and APOEr2 receptors. RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alzheimer Disease Limits: Animals / Female / Humans / Male Language: En Journal: Nat Med Journal subject: BIOLOGIA MOLECULAR / MEDICINA Year: 2023 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alzheimer Disease Limits: Animals / Female / Humans / Male Language: En Journal: Nat Med Journal subject: BIOLOGIA MOLECULAR / MEDICINA Year: 2023 Document type: Article Affiliation country: