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Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer's disease.
Crist, Angela M; Hinkle, Kelly M; Wang, Xue; Moloney, Christina M; Matchett, Billie J; Labuzan, Sydney A; Frankenhauser, Isabelle; Azu, Nkem O; Liesinger, Amanda M; Lesser, Elizabeth R; Serie, Daniel J; Quicksall, Zachary S; Patel, Tulsi A; Carnwath, Troy P; DeTure, Michael; Tang, Xiaojia; Petersen, Ronald C; Duara, Ranjan; Graff-Radford, Neill R; Allen, Mariet; Carrasquillo, Minerva M; Li, Hu; Ross, Owen A; Ertekin-Taner, Nilüfer; Dickson, Dennis W; Asmann, Yan W; Carter, Rickey E; Murray, Melissa E.
Afiliación
  • Crist AM; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Hinkle KM; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Wang X; Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
  • Moloney CM; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Matchett BJ; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Labuzan SA; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Frankenhauser I; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Azu NO; Paracelsus Medical Private University, Salzburg, Austria.
  • Liesinger AM; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Lesser ER; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Serie DJ; Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
  • Quicksall ZS; Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
  • Patel TA; Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
  • Carnwath TP; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • DeTure M; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Tang X; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Petersen RC; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Duara R; Department of Neurology, Mayo Clinic, Rochester, MN, USA.
  • Graff-Radford NR; Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA.
  • Allen M; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
  • Carrasquillo MM; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Li H; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Ross OA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
  • Ertekin-Taner N; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Dickson DW; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Asmann YW; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
  • Carter RE; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Murray ME; Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
Nat Commun ; 12(1): 2311, 2021 04 19.
Article en En | MEDLINE | ID: mdl-33875655
Selective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer's disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Corteza Cerebral / Perfilación de la Expresión Génica / Enfermedad de Alzheimer / Hipocampo Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Corteza Cerebral / Perfilación de la Expresión Génica / Enfermedad de Alzheimer / Hipocampo Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido