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Sökning: WFRF:(Bridel Claire) > (2024) > CSF protein ratios ...

  • Mravinacová, SáraKTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab (författare)

CSF protein ratios with enhanced potential to reflect Alzheimer’s disease pathology and neurodegeneration

  • Artikel/kapitelEngelska2024

Förlag, utgivningsår, omfång ...

  • Springer Nature,2024
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:kth-344014
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-344014URI
  • https://doi.org/10.1186/s13024-024-00705-zDOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:154939952URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • QC 20240301
  • Background: Amyloid and tau aggregates are considered to cause neurodegeneration and consequently cognitive decline in individuals with Alzheimer’s disease (AD). Here, we explore the potential of cerebrospinal fluid (CSF) proteins to reflect AD pathology and cognitive decline, aiming to identify potential biomarkers for monitoring outcomes of disease-modifying therapies targeting these aggregates. Method: We used a multiplex antibody-based suspension bead array to measure the levels of 49 proteins in CSF from the Swedish GEDOC memory clinic cohort at the Karolinska University Hospital. The cohort comprised 148 amyloid- and tau-negative individuals (A-T-) and 65 amyloid- and tau-positive individuals (A+T+). An independent sample set of 26 A-T- and 26 A+T+ individuals from the Amsterdam Dementia Cohort was used for validation. The measured proteins were clustered based on their correlation to CSF amyloid beta peptides, tau and NfL levels. Further, we used support vector machine modelling to identify protein pairs, matched based on their cluster origin, that reflect AD pathology and cognitive decline with improved performance compared to single proteins. Results: The protein-clustering revealed 11 proteins strongly correlated to t-tau and p-tau (tau-associated group), including mainly synaptic proteins previously found elevated in AD such as NRGN, GAP43 and SNCB. Another 16 proteins showed predominant correlation with Aβ42 (amyloid-associated group), including PTPRN2, NCAN and CHL1. Support vector machine modelling revealed that proteins from the two groups combined in pairs discriminated A-T- from A+T+ individuals with higher accuracy compared to single proteins, as well as compared to protein pairs composed of proteins originating from the same group. Moreover, combining the proteins from different groups in ratios (tau-associated protein/amyloid-associated protein) significantly increased their correlation to cognitive decline measured with cognitive scores. The results were validated in an independent cohort. Conclusions: Combining brain-derived proteins in pairs largely enhanced their capacity to discriminate between AD pathology-affected and unaffected individuals and increased their correlation to cognitive decline, potentially due to adjustment of inter-individual variability. With these results, we highlight the potential of protein pairs to monitor neurodegeneration and thereby possibly the efficacy of AD disease-modifying therapies.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Alanko, VilmaDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden (författare)
  • Bergström, SofiaKTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik(Swepub:kth)u1ugb8pi (författare)
  • Bridel, ClaireNeurochemistry Lab, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, Netherlands (författare)
  • Pijnenburg, YolandeDepartment of Neurology, Alzheimer Centre, Amsterdam UMC, Vrije Universiteit, Amsterdam, Netherlands (författare)
  • Hagman, GöranDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden (författare)
  • Kivipelto, MiiaDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Ageing Epidemiology (AGE) Research Unit, Imperial College London, London, United Kingdom; Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden; Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland (författare)
  • Teunissen, CharlotteNeurochemistry Lab, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, Netherlands (författare)
  • Nilsson, PeterKTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik(Swepub:kth)u1ws88sk (författare)
  • Matton, AnnaDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Ageing Epidemiology (AGE) Research Unit, Imperial College London, London, United Kingdom (författare)
  • Månberg, Anna,1985-KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik(Swepub:kth)u1g5roxd (författare)
  • KTHAffinitets-proteomik (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Molecular Neurodegeneration: Springer Nature19:11750-1326

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