| Title: |
Cerebrospinal fluid proteomic profiling of cognitively unimpaired individuals with suspected non-Alzheimer's disease pathophysiology |
| Authors: |
Delvenne, Aurore; Gobom, Johan; Reus, Lianne M; Dobricic, Valerija; ten Kate, Mara; Schindler, Suzanne E; Ramakers, Inez; Tijms, Betty M; Vandenberghe, Rik; Schaeverbeke, Jolien; Martinez-Lage, Pablo; Tainta, Mikel; Teunissen, Charlotte E; Popp, Julius; Peyratout, Gwendoline; Tsolaki, Magda; Freund-Levi, Yvonne; Lovestone, Simon; Streffer, Johannes; Barkhof, Frederik; Bertram, Lars; Blennow, Kaj; Zetterberg, Henrik; Visser, Pieter Jelle; Vos, Stephanie J B |
| Contributors: |
ZonMw; Netherlands Organisation for Health Research and Development; Janssen Pharmaceutica N.V.; European Medical Information Framework for Alzheimer's disease; Innovative Medicines Initiative Joint Undertaking under EMIF; European Union's Seventh Framework Programme; European Federation of Pharmaceutical Industries and Associations; DESCRIPA; European Commission; EDAR; European Commission within the 5th framework programme; Department of Health of the Basque Government; Provincial Government of Gipuzkoa; Kutxa Fundazioa; Carlos III Institute of Health; Swiss National Research Foundation; Knight Alzheimer Disease Research Centre; National Institute on Aging; National Institute for Health and Care Research; biomedical research centre at University College London Hospitals; Wallenberg Scholar; Swedish Research Council; European Union’s Horizon Europe research and innovation programme; Swedish State Support for Clinical Research; Alzheimer Drug Discovery Foundation; Alzheimer's Association; Bluefield Project, Cure Alzheimer’s Fund; Olav Thon Foundation; Erling-Persson Family Foundation; Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden; European Union’s Horizon 2020 research and innovation programme; Marie Skłodowska-Curie; European Union Joint Programme—Neurodegenerative Disease Research; National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre; UK Dementia Research Institute at University College London |
| Source: |
Brain Communications ; volume 7, issue 4 ; ISSN 2632-1297 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2025 |
| Description: |
Suspected non-Alzheimer's disease pathophysiology (SNAP) is a biomarker-based concept describing individuals with abnormal tau and/or neurodegeneration markers but normal amyloid levels. SNAP is common in individuals with normal cognition (NC), but its underlying pathophysiology is understudied, while being relevant for clinical trial design and treatment approaches. We aimed to investigate the pathophysiology of individuals with NC who are amyloid-negative and tau-positive (SNAP) through cerebrospinal fluid (CSF) proteomics. Two hundred and ninety-one individuals with NC were classified based on CSF amyloid β1-42 and phosphorylated tau 181, as amyloid-negative/tau-negative (controls), amyloid-negative/tau-positive (SNAP), amyloid-positive/tau-negative and amyloid-positive/tau-positive. We measured 3102 proteins in CSF using tandem mass tag proteomic analyses. We compared protein abundance between groups using analysis of covariance and identified enriched biological pathways using Gene Ontology. We also examined differences between groups in genetic risk for Alzheimer’s disease, estimated using polygenic risk scores based on genome-wide association study data. SNAP individuals with NC showed mostly increased protein levels (n = 360) compared with controls, mainly associated with neuroplasticity, angiogenesis, and protein modification and degradation. The proteomic profile of SNAP was similar to that of amyloid-positive/tau-positive individuals, while distinct from amyloid-positive/tau-negative individuals, who showed mainly decreased proteins associated with neuroplasticity. Higher levels of amyloid β1-40 and amyloid β1-42 were observed in SNAP compared with the three other groups. Polygenic risk scores analyses showed no significant differences between SNAP, amyloid-positive/tau-negative, and amyloid-positive/tau-positive individuals, while SNAP showed some genetic differences from controls, which were driven by APOE. Individuals with NC and SNAP or amyloid-positive/tau-positive status showed similar ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/braincomms/fcaf253 |
| DOI: |
10.1093/braincomms/fcaf253/63537563/fcaf253.pdf |
| Availability: |
https://doi.org/10.1093/braincomms/fcaf253; https://academic.oup.com/braincomms/advance-article-pdf/doi/10.1093/braincomms/fcaf253/63537563/fcaf253.pdf; https://academic.oup.com/braincomms/article-pdf/7/4/fcaf253/63537563/fcaf253.pdf |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.8D741D0 |
| Database: |
BASE |