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Spatial proteomics of hippocampal subfield-specific pathology in Alzheimer's disease and primary age-related tauopathy.
Walker, Jamie M; Orr, Miranda E; Orr, Timothy C; Thorn, Emma L; Christie, Thomas D; Yokoda, Raquel T; Vij, Meenakshi; Ehrenberg, Alexander J; Marx, Gabriel A; McKenzie, Andrew T; Kauffman, Justin; Selmanovic, Enna; Wisniewski, Thomas; Drummond, Eleanor; White, Charles L; Crary, John F; Farrell, Kurt; Kautz, Tiffany F; Daoud, Elena V; Richardson, Timothy E.
Afiliación
  • Walker JM; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Orr ME; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Orr TC; Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Thorn EL; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, Texas, USA.
  • Christie TD; Section of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
  • Yokoda RT; Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
  • Vij M; Salisbury VA Medical Center, Salisbury, North Carolina, USA.
  • Ehrenberg AJ; Section of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
  • Marx GA; Department of Healthcare Innovations, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
  • McKenzie AT; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Kauffman J; Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Selmanovic E; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Wisniewski T; Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Drummond E; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • White CL; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Crary JF; Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
  • Farrell K; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, California, USA.
  • Kautz TF; Innovative Genomics Institute, University of California, Berkeley, Berkeley, California, USA.
  • Daoud EV; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Richardson TE; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Alzheimers Dement ; 20(2): 783-797, 2024 Feb.
Article en En | MEDLINE | ID: mdl-37777848
INTRODUCTION: Alzheimer's disease (AD) and primary age-related tauopathy (PART) both harbor 3R/4R hyperphosphorylated-tau (p-tau)-positive neurofibrillary tangles (NFTs) but differ in the spatial p-tau development in the hippocampus. METHODS: Using Nanostring GeoMx Digital Spatial Profiling, we compared protein expression within hippocampal subregions in NFT-bearing and non-NFT-bearing neurons in AD (n = 7) and PART (n = 7) subjects. RESULTS: Proteomic measures of synaptic health were inversely correlated with the subregional p-tau burden in AD and PART, and there were numerous differences in proteins involved in proteostasis, amyloid beta (Aß) processing, inflammation, microglia, oxidative stress, and neuronal/synaptic health between AD and PART and between definite PART and possible PART. DISCUSSION: These results suggest subfield-specific proteome differences that may explain some of the differences in Aß and p-tau distribution and apparent pathogenicity. In addition, hippocampal neurons in possible PART may have more in common with AD than with definite PART, highlighting the importance of Aß in the pathologic process. HIGHLIGHTS: Synaptic health is inversely correlated with local p-tau burden. The proteome of NFT- and non-NFT-bearing neurons is influenced by the presence of Aß in the hippocampus. Neurons in possible PART cases share more proteomic similarities with neurons in ADNC than they do with neurons in definite PART cases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tauopatías / Enfermedad de Alzheimer 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: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tauopatías / Enfermedad de Alzheimer Límite: Humans Idioma: En Revista: Alzheimers Dement Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos