Proteomic analysis of Down syndrome cerebrospinal fluid compared to late-onset and autosomal dominant Alzheimer's disease
Montoliu Gaya, Laia (Department of Psychiatry and Neurochemistry. Institute of Neuroscience & Physiology. The Sahlgrenska Academy at the University of Gothenburg)
Alcolea, Daniel (Institut de Recerca Sant Pau)
Ashton, Nicholas J. (The Sahlgrenska Academy at the University of Gothenburg)
Belbin, Olivia (Institut de Recerca Sant Pau)
Fuchs, Johannes (University of Gothenburg)
Nilsson, Johanna (The Sahlgrenska Academy at the University of Gothenburg)
Barroeta, Isabel (Institut de Recerca Sant Pau)
Lantero-Rodríguez, Juan (The Sahlgrenska Academy at the University of Gothenburg)
Videla Toro, Laura (Institut de Recerca Sant Pau)
Benejam, Bessy (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Blennow, Kaj (Sahlgrenska University Hospital)
Levey, Allan I. (Emory University School of Medicine)
Carmona Iragui, Maria (Institut de Recerca Sant Pau)
Gobom, Johan (The Sahlgrenska Academy at the University of Gothenburg)
Lleó, Alberto (Institut de Recerca Sant Pau)
Wisniewski, Thomas (NYU Grossman School of Medicine)
Zetterberg, Henrik (University of Wisconsin School of Medicine and Public Health)
Fortea, Juan (Institut de Recerca Sant Pau)
Johnson, Erik C.B. (Emory University School of Medicine)
Bian, Shijia (Emory University)
Dammer, Eric B. (Goizueta Alzheimer's Disease Research Center)
Sauer, Mathias (The Sahlgrenska Academy at the University of Gothenburg)
Martá Ariza, Mitchell (Universitat Autònoma de Barcelona)
Watson, Caroline M. (Emory University School of Medicine)
Ping, Lingyan (Emory University School of Medicine)
Duong, Duc M. (Goizueta Alzheimer's Disease Research Center)
Roberts, Blaine R. (Emory University School of Medicine)
Seyfried, Nicholas T. (Emory University School of Medicine)

Fecha:	2025
Resumen:	Almost all individuals with Down Syndrome (DS) develop Alzheimer's disease (AD) by mid to late life. However, the degree to which AD in DS shares pathological changes with sporadic late-onset AD (LOAD) and autosomal dominant AD (ADAD) beyond core AD biomarkers such as amyloid-β (Aβ) and tau is unknown. Here, we used proteomics of cerebrospinal fluid from individuals with DS (n = 229) in the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) cohort to assess the evolution of AD pathophysiology from asymptomatic to dementia stages and compared the proteomic biomarker changes in DS to those observed in LOAD and ADAD. Although many proteomic alterations were shared across DS, LOAD, and ADAD, DS demonstrated more severe changes in immune-related proteins, extracellular matrix pathways, and plasma proteins likely related to blood-brain barrier dysfunction compared to LOAD. These changes were present in young adults with DS prior to the onset of Aβ or tau pathology, suggesting they are associated with trisomy 21 and may serve as risk factors for DSAD. DSAD showed an earlier increase in markers of axonal and white matter pathology and earlier changes in markers potentially associated with cerebral amyloid angiopathy compared to ADAD. The unique features of DSAD may have important implications for treatment strategies in this population.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Adult ; Age of Onset ; Aged ; Alzheimer Disease ; Amyloid beta-Peptides ; Biomarkers ; Down Syndrome ; Female ; Humans ; Male ; Middle Aged ; Proteome ; Proteomics ; tau Proteins ; Young Adult
Publicado en:	Nature communications, Vol. 16, Num. 1 (December 2025) , art. 6003, ISSN 2041-1723

DOI: 10.1038/s41467-025-61054-z
PMID: 40595720

20 p, 4.1 MB

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