Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease
- Autores
- Johnson, Erik C. B.; Bian, Shijia; Haque, Rafi U.; Carter, E. Kathleen; Watson, Caroline M.; Gordon, Brian A.; Ping, Lingyan; Duong, Duc M.; Epstein, Michael P.; McDade, Eric; Barthélemy, Nicolas R.; Karch, Celeste M.; Xiong, Chengjie; Cruchaga, Carlos; Perrin, Richard J.; Wingo, Aliza P.; Wingo, Thomas S.; Chhatwal, Jasmeer P.; Day, Gregory S.; Noble, James M.; Berman, Sarah B.; Martins, Ralph; Graff Radford, Neill R.; Surace, Ezequiel Ignacio; Ortiz, Ana Luisa Sosa; Daniels, Alisha; Courtney, Laura; Supnet Bell, Charlene; Xu, Jinbin; Ringman, John
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation of the amyloid-β (Aβ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)—are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of Aβ plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning six decades. SMOC1 and SPON1 proteins associated with Aβ plaques were elevated in AD CSF nearly 30 years before the onset of symptoms, followed by changes in synaptic proteins, metabolic proteins, axonal proteins, inflammatory proteins and finally decreases in neurosecretory proteins. The proteome discriminated mutation carriers from noncarriers before symptom onset as well or better than Aβ and tau measures. Our results highlight the multifaceted landscape of AD pathophysiology and its temporal evolution. Such knowledge will be critical for developing precision therapeutic interventions and biomarkers for AD beyond those associated with Aβ and tau.
Fil: Johnson, Erik C. B.. University of Emory; Estados Unidos
Fil: Bian, Shijia. University of Emory; Estados Unidos
Fil: Haque, Rafi U.. University of Emory; Estados Unidos
Fil: Carter, E. Kathleen. University of Emory; Estados Unidos
Fil: Watson, Caroline M.. University of Emory; Estados Unidos
Fil: Gordon, Brian A.. Washington University in St. Louis; Estados Unidos
Fil: Ping, Lingyan. University of Emory; Estados Unidos
Fil: Duong, Duc M.. University of Emory; Estados Unidos
Fil: Epstein, Michael P.. University of Emory; Estados Unidos
Fil: McDade, Eric. Washington University in St. Louis; Estados Unidos
Fil: Barthélemy, Nicolas R.. Washington University in St. Louis; Estados Unidos
Fil: Karch, Celeste M.. Washington University in St. Louis; Estados Unidos
Fil: Xiong, Chengjie. Washington University in St. Louis; Estados Unidos
Fil: Cruchaga, Carlos. Washington University in St. Louis; Estados Unidos
Fil: Perrin, Richard J.. Washington University in St. Louis; Estados Unidos
Fil: Wingo, Aliza P.. Washington University in St. Louis; Estados Unidos
Fil: Wingo, Thomas S.. University of Emory; Estados Unidos
Fil: Chhatwal, Jasmeer P.. Harvard Medical School; Estados Unidos
Fil: Day, Gregory S.. University of Emory; Estados Unidos
Fil: Noble, James M.. Harvard Medical School; Estados Unidos
Fil: Berman, Sarah B.. Mayo Clinic; Estados Unidos
Fil: Martins, Ralph. Edith Cowan University; Australia
Fil: Graff Radford, Neill R.. Univeristy of Pittsburgh. School of Medicine; Estados Unidos. Mayo Clinic; Estados Unidos
Fil: Surace, Ezequiel Ignacio. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ortiz, Ana Luisa Sosa. Washington University in St. Louis; Estados Unidos
Fil: Daniels, Alisha. Washington University in St. Louis; Estados Unidos
Fil: Courtney, Laura. Washington University in St. Louis; Estados Unidos
Fil: Supnet Bell, Charlene. Washington University in St. Louis; Estados Unidos
Fil: Xu, Jinbin. No especifíca;
Fil: Ringman, John. No especifíca; - Materia
-
BIOMARCADORES
ALZHEIMER
PROTEOMICA
GENETICA - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/240957
Ver los metadatos del registro completo
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Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s diseaseJohnson, Erik C. B.Bian, ShijiaHaque, Rafi U.Carter, E. KathleenWatson, Caroline M.Gordon, Brian A.Ping, LingyanDuong, Duc M.Epstein, Michael P.McDade, EricBarthélemy, Nicolas R.Karch, Celeste M.Xiong, ChengjieCruchaga, CarlosPerrin, Richard J.Wingo, Aliza P.Wingo, Thomas S.Chhatwal, Jasmeer P.Day, Gregory S.Noble, James M.Berman, Sarah B.Martins, RalphGraff Radford, Neill R.Surace, Ezequiel IgnacioOrtiz, Ana Luisa SosaDaniels, AlishaCourtney, LauraSupnet Bell, CharleneXu, JinbinRingman, JohnBIOMARCADORESALZHEIMERPROTEOMICAGENETICAhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation of the amyloid-β (Aβ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)—are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of Aβ plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning six decades. SMOC1 and SPON1 proteins associated with Aβ plaques were elevated in AD CSF nearly 30 years before the onset of symptoms, followed by changes in synaptic proteins, metabolic proteins, axonal proteins, inflammatory proteins and finally decreases in neurosecretory proteins. The proteome discriminated mutation carriers from noncarriers before symptom onset as well or better than Aβ and tau measures. Our results highlight the multifaceted landscape of AD pathophysiology and its temporal evolution. Such knowledge will be critical for developing precision therapeutic interventions and biomarkers for AD beyond those associated with Aβ and tau.Fil: Johnson, Erik C. B.. University of Emory; Estados UnidosFil: Bian, Shijia. University of Emory; Estados UnidosFil: Haque, Rafi U.. University of Emory; Estados UnidosFil: Carter, E. Kathleen. University of Emory; Estados UnidosFil: Watson, Caroline M.. University of Emory; Estados UnidosFil: Gordon, Brian A.. Washington University in St. Louis; Estados UnidosFil: Ping, Lingyan. University of Emory; Estados UnidosFil: Duong, Duc M.. University of Emory; Estados UnidosFil: Epstein, Michael P.. University of Emory; Estados UnidosFil: McDade, Eric. Washington University in St. Louis; Estados UnidosFil: Barthélemy, Nicolas R.. Washington University in St. Louis; Estados UnidosFil: Karch, Celeste M.. Washington University in St. Louis; Estados UnidosFil: Xiong, Chengjie. Washington University in St. Louis; Estados UnidosFil: Cruchaga, Carlos. Washington University in St. Louis; Estados UnidosFil: Perrin, Richard J.. Washington University in St. Louis; Estados UnidosFil: Wingo, Aliza P.. Washington University in St. Louis; Estados UnidosFil: Wingo, Thomas S.. University of Emory; Estados UnidosFil: Chhatwal, Jasmeer P.. Harvard Medical School; Estados UnidosFil: Day, Gregory S.. University of Emory; Estados UnidosFil: Noble, James M.. Harvard Medical School; Estados UnidosFil: Berman, Sarah B.. Mayo Clinic; Estados UnidosFil: Martins, Ralph. Edith Cowan University; AustraliaFil: Graff Radford, Neill R.. Univeristy of Pittsburgh. School of Medicine; Estados Unidos. Mayo Clinic; Estados UnidosFil: Surace, Ezequiel Ignacio. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ortiz, Ana Luisa Sosa. Washington University in St. Louis; Estados UnidosFil: Daniels, Alisha. Washington University in St. Louis; Estados UnidosFil: Courtney, Laura. Washington University in St. Louis; Estados UnidosFil: Supnet Bell, Charlene. Washington University in St. Louis; Estados UnidosFil: Xu, Jinbin. No especifíca;Fil: Ringman, John. No especifíca;Nature Publishing Group2023-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/240957Johnson, Erik C. B.; Bian, Shijia; Haque, Rafi U.; Carter, E. Kathleen; Watson, Caroline M.; et al.; Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease; Nature Publishing Group; Nature Medicine; 29; 8; 8-2023; 1979-19881078-8956CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41591-023-02476-4info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41591-023-02476-4info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:53Zoai:ri.conicet.gov.ar:11336/240957instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:44:53.453CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease |
| title |
Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease |
| spellingShingle |
Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease Johnson, Erik C. B. BIOMARCADORES ALZHEIMER PROTEOMICA GENETICA |
| title_short |
Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease |
| title_full |
Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease |
| title_fullStr |
Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease |
| title_full_unstemmed |
Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease |
| title_sort |
Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease |
| dc.creator.none.fl_str_mv |
Johnson, Erik C. B. Bian, Shijia Haque, Rafi U. Carter, E. Kathleen Watson, Caroline M. Gordon, Brian A. Ping, Lingyan Duong, Duc M. Epstein, Michael P. McDade, Eric Barthélemy, Nicolas R. Karch, Celeste M. Xiong, Chengjie Cruchaga, Carlos Perrin, Richard J. Wingo, Aliza P. Wingo, Thomas S. Chhatwal, Jasmeer P. Day, Gregory S. Noble, James M. Berman, Sarah B. Martins, Ralph Graff Radford, Neill R. Surace, Ezequiel Ignacio Ortiz, Ana Luisa Sosa Daniels, Alisha Courtney, Laura Supnet Bell, Charlene Xu, Jinbin Ringman, John |
| author |
Johnson, Erik C. B. |
| author_facet |
Johnson, Erik C. B. Bian, Shijia Haque, Rafi U. Carter, E. Kathleen Watson, Caroline M. Gordon, Brian A. Ping, Lingyan Duong, Duc M. Epstein, Michael P. McDade, Eric Barthélemy, Nicolas R. Karch, Celeste M. Xiong, Chengjie Cruchaga, Carlos Perrin, Richard J. Wingo, Aliza P. Wingo, Thomas S. Chhatwal, Jasmeer P. Day, Gregory S. Noble, James M. Berman, Sarah B. Martins, Ralph Graff Radford, Neill R. Surace, Ezequiel Ignacio Ortiz, Ana Luisa Sosa Daniels, Alisha Courtney, Laura Supnet Bell, Charlene Xu, Jinbin Ringman, John |
| author_role |
author |
| author2 |
Bian, Shijia Haque, Rafi U. Carter, E. Kathleen Watson, Caroline M. Gordon, Brian A. Ping, Lingyan Duong, Duc M. Epstein, Michael P. McDade, Eric Barthélemy, Nicolas R. Karch, Celeste M. Xiong, Chengjie Cruchaga, Carlos Perrin, Richard J. Wingo, Aliza P. Wingo, Thomas S. Chhatwal, Jasmeer P. Day, Gregory S. Noble, James M. Berman, Sarah B. Martins, Ralph Graff Radford, Neill R. Surace, Ezequiel Ignacio Ortiz, Ana Luisa Sosa Daniels, Alisha Courtney, Laura Supnet Bell, Charlene Xu, Jinbin Ringman, John |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
BIOMARCADORES ALZHEIMER PROTEOMICA GENETICA |
| topic |
BIOMARCADORES ALZHEIMER PROTEOMICA GENETICA |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation of the amyloid-β (Aβ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)—are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of Aβ plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning six decades. SMOC1 and SPON1 proteins associated with Aβ plaques were elevated in AD CSF nearly 30 years before the onset of symptoms, followed by changes in synaptic proteins, metabolic proteins, axonal proteins, inflammatory proteins and finally decreases in neurosecretory proteins. The proteome discriminated mutation carriers from noncarriers before symptom onset as well or better than Aβ and tau measures. Our results highlight the multifaceted landscape of AD pathophysiology and its temporal evolution. Such knowledge will be critical for developing precision therapeutic interventions and biomarkers for AD beyond those associated with Aβ and tau. Fil: Johnson, Erik C. B.. University of Emory; Estados Unidos Fil: Bian, Shijia. University of Emory; Estados Unidos Fil: Haque, Rafi U.. University of Emory; Estados Unidos Fil: Carter, E. Kathleen. University of Emory; Estados Unidos Fil: Watson, Caroline M.. University of Emory; Estados Unidos Fil: Gordon, Brian A.. Washington University in St. Louis; Estados Unidos Fil: Ping, Lingyan. University of Emory; Estados Unidos Fil: Duong, Duc M.. University of Emory; Estados Unidos Fil: Epstein, Michael P.. University of Emory; Estados Unidos Fil: McDade, Eric. Washington University in St. Louis; Estados Unidos Fil: Barthélemy, Nicolas R.. Washington University in St. Louis; Estados Unidos Fil: Karch, Celeste M.. Washington University in St. Louis; Estados Unidos Fil: Xiong, Chengjie. Washington University in St. Louis; Estados Unidos Fil: Cruchaga, Carlos. Washington University in St. Louis; Estados Unidos Fil: Perrin, Richard J.. Washington University in St. Louis; Estados Unidos Fil: Wingo, Aliza P.. Washington University in St. Louis; Estados Unidos Fil: Wingo, Thomas S.. University of Emory; Estados Unidos Fil: Chhatwal, Jasmeer P.. Harvard Medical School; Estados Unidos Fil: Day, Gregory S.. University of Emory; Estados Unidos Fil: Noble, James M.. Harvard Medical School; Estados Unidos Fil: Berman, Sarah B.. Mayo Clinic; Estados Unidos Fil: Martins, Ralph. Edith Cowan University; Australia Fil: Graff Radford, Neill R.. Univeristy of Pittsburgh. School of Medicine; Estados Unidos. Mayo Clinic; Estados Unidos Fil: Surace, Ezequiel Ignacio. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ortiz, Ana Luisa Sosa. Washington University in St. Louis; Estados Unidos Fil: Daniels, Alisha. Washington University in St. Louis; Estados Unidos Fil: Courtney, Laura. Washington University in St. Louis; Estados Unidos Fil: Supnet Bell, Charlene. Washington University in St. Louis; Estados Unidos Fil: Xu, Jinbin. No especifíca; Fil: Ringman, John. No especifíca; |
| description |
Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation of the amyloid-β (Aβ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)—are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of Aβ plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning six decades. SMOC1 and SPON1 proteins associated with Aβ plaques were elevated in AD CSF nearly 30 years before the onset of symptoms, followed by changes in synaptic proteins, metabolic proteins, axonal proteins, inflammatory proteins and finally decreases in neurosecretory proteins. The proteome discriminated mutation carriers from noncarriers before symptom onset as well or better than Aβ and tau measures. Our results highlight the multifaceted landscape of AD pathophysiology and its temporal evolution. Such knowledge will be critical for developing precision therapeutic interventions and biomarkers for AD beyond those associated with Aβ and tau. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-08 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
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http://hdl.handle.net/11336/240957 Johnson, Erik C. B.; Bian, Shijia; Haque, Rafi U.; Carter, E. Kathleen; Watson, Caroline M.; et al.; Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease; Nature Publishing Group; Nature Medicine; 29; 8; 8-2023; 1979-1988 1078-8956 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/240957 |
| identifier_str_mv |
Johnson, Erik C. B.; Bian, Shijia; Haque, Rafi U.; Carter, E. Kathleen; Watson, Caroline M.; et al.; Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease; Nature Publishing Group; Nature Medicine; 29; 8; 8-2023; 1979-1988 1078-8956 CONICET Digital CONICET |
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eng |
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eng |
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Nature Publishing Group |
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Nature Publishing Group |
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