Spatial proteomics of hippocampal subfield-specific pathology in Alzheimer's disease and primary age-related tauopathy.

Autor:	Walker JM; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, Texas, USA., Orr ME; Section of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.; Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.; Salisbury VA Medical Center, Salisbury, North Carolina, USA., Orr TC; Section of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.; Department of Healthcare Innovations, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA., Thorn EL; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Christie TD; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Yokoda RT; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Vij M; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Ehrenberg AJ; Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, California, USA.; Innovative Genomics Institute, University of California, Berkeley, Berkeley, California, USA., Marx GA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Artificial Intelligence & Human Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Ronal M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., McKenzie AT; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Artificial Intelligence & Human Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Ronal M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Kauffman J; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Artificial Intelligence & Human Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Ronal M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Selmanovic E; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Wisniewski T; Department of Pathology, New York University Grossman School of Medicine, New York, New York, USA.; Department of Psychiatry, New York University Grossman School of Medicine, New York, New York, USA.; Center for Cognitive Neurology, Department of Neurology, New York University Grossman School of Medicine, New York, New York, USA., Drummond E; Brain & Mind Center and School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, Australia., White CL 3rd; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA., Crary JF; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Artificial Intelligence & Human Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Ronal M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Farrell K; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Artificial Intelligence & Human Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Ronal M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Kautz TF; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, Texas, USA., Daoud EV; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA., Richardson TE; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Jazyk:	angličtina
Zdroj:	Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2024 Feb; Vol. 20 (2), pp. 783-797. Date of Electronic Publication: 2023 Sep 30.
DOI:	10.1002/alz.13484
Abstrakt:	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 (Aβ) 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 Aβ 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 Aβ 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 Aβ 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. (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Plný text