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Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage.
Joseph-Mathurin, Nelly; Feldman, Rebecca L; Lu, Ruijin; Shirzadi, Zahra; Toomer, Carmen; Saint Clair, Junie R; Ma, Yinjiao; McKay, Nicole S; Strain, Jeremy F; Kilgore, Collin; Friedrichsen, Karl A; Chen, Charles D; Gordon, Brian A; Chen, Gengsheng; Hornbeck, Russ C; Massoumzadeh, Parinaz; McCullough, Austin A; Wang, Qing; Li, Yan; Wang, Guoqiao; Keefe, Sarah J; Schultz, Stephanie A; Cruchaga, Carlos; Preboske, Gregory M; Jack, Clifford R; Llibre-Guerra, Jorge J; Allegri, Ricardo F; Ances, Beau M; Berman, Sarah B; Brooks, William S; Cash, David M; Day, Gregory S; Fox, Nick C; Fulham, Michael; Ghetti, Bernardino; Johnson, Keith A; Jucker, Mathias; Klunk, William E; la Fougère, Christian; Levin, Johannes; Niimi, Yoshiki; Oh, Hwamee; Perrin, Richard J; Reischl, Gerald; Ringman, John M; Saykin, Andrew J; Schofield, Peter R; Su, Yi; Supnet-Bell, Charlene; Vöglein, Jonathan.
Afiliación
  • Joseph-Mathurin N; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Feldman RL; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Lu R; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Shirzadi Z; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Toomer C; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Saint Clair JR; Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Ma Y; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • McKay NS; Meharry School of Medicine, Meharry College, Nashville, Tennessee, USA.
  • Strain JF; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Kilgore C; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Friedrichsen KA; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Chen CD; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Gordon BA; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Chen G; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Hornbeck RC; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Massoumzadeh P; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • McCullough AA; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Wang Q; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Li Y; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Wang G; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Keefe SJ; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Schultz SA; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Cruchaga C; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Preboske GM; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Jack CR; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Llibre-Guerra JJ; Mayo Clinic, Rochester, Minnesota, USA.
  • Allegri RF; Mayo Clinic, Rochester, Minnesota, USA.
  • Ances BM; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Berman SB; Institute for Neurological Research FLENI, Montañeses, Buenos Aires, Argentina.
  • Brooks WS; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
  • Cash DM; University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
  • Day GS; Neuroscience Research Australia, Sydney, NSW, Australia.
  • Fox NC; University of New South Wales, Sydney, NSW, Australia.
  • Fulham M; UK Dementia Research Institute and Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Ghetti B; Mayo Clinic, Jacksonville, Florida, USA.
  • Johnson KA; UK Dementia Research Institute and Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Jucker M; Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
  • Klunk WE; Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • la Fougère C; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Levin J; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
  • Niimi Y; Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
  • Oh H; University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
  • Perrin RJ; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
  • Reischl G; University hospital Tübingen, Tübingen, Germany.
  • Ringman JM; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
  • Saykin AJ; Ludwig Maximilian University of Munich, Munich, Germany.
  • Schofield PR; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
  • Su Y; The University of Tokyo, Bunkyo City, Tokyo, Japan.
  • Supnet-Bell C; Brown University, Providence, Rhode Island, USA.
  • Vöglein J; Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
Alzheimers Dement ; 20(4): 2680-2697, 2024 04.
Article en En | MEDLINE | ID: mdl-38380882
ABSTRACT

INTRODUCTION:

Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages.

METHODS:

Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments. We cross-sectionally evaluated regional Pittsburgh compound B-positron emission tomography uptake, magnetic resonance imaging markers of SVD (diffusion tensor imaging-based white matter injury, white matter hyperintensity volumes, and microhemorrhages), and cognition.

RESULTS:

Postcodon 200 carriers had lower amyloid burden in all regions but worse markers of SVD and worse Clinical Dementia Rating® scores compared to precodon 200 carriers as a function of estimated years to symptom onset. Markers of SVD partially mediated the mutation position effects on clinical measures.

DISCUSSION:

We demonstrated the genotypic variability behind spatiotemporal amyloidosis, SVD, and clinical presentation in DIAD, which may inform patient prognosis and clinical trials. HIGHLIGHTS Mutation position influences Aß burden, SVD, and dementia. PSEN1 pre-200 group had stronger associations between Aß burden and disease stage. PSEN1 post-200 group had stronger associations between SVD markers and disease stage. PSEN1 post-200 group had worse dementia score than pre-200 in late disease stage. Diffusion tensor imaging-based SVD markers mediated mutation position effects on dementia in the late stage.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Enfermedades de los Pequeños Vasos Cerebrales / Amiloidosis Límite: Humans Idioma: En Revista: Alzheimers Dement Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Enfermedades de los Pequeños Vasos Cerebrales / Amiloidosis Límite: Humans Idioma: En Revista: Alzheimers Dement Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos