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Combination of plasma amyloid beta(1-42/1-40)and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology

Verberk, Inge M.W. (författare)
Vrije Universiteit Amsterdam
Thijssen, Elisabeth (författare)
Vrije Universiteit Amsterdam
Koelewijn, Jannet (författare)
Vrije Universiteit Amsterdam
visa fler...
Mauroo, Kimberley (författare)
ADx NeuroSciences
Vanbrabant, Jeroen (författare)
ADx NeuroSciences
De Wilde, Arno (författare)
Vrije Universiteit Amsterdam
Zwan, Marissa D. (författare)
Vrije Universiteit Amsterdam
Verfaillie, Sander C.J. (författare)
Vrije Universiteit Amsterdam
Ossenkoppele, Rik (författare)
Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Vrije Universiteit Amsterdam
Barkhof, Frederik (författare)
University College London
Van Berckel, Bart N.M. (författare)
Vrije Universiteit Amsterdam
Scheltens, Philip (författare)
Vrije Universiteit Amsterdam
Van Der Flier, Wiesje M. (författare)
Vrije Universiteit Amsterdam
Stoops, Erik (författare)
ADx NeuroSciences
Vanderstichele, Hugo M. (författare)
ADx NeuroSciences
Teunissen, Charlotte E. (författare)
Vrije Universiteit Amsterdam
visa färre...
 (creator_code:org_t)
2020-09-28
2020
Engelska.
Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Background: Blood-based biomarkers for Alzheimer's disease (AD) might facilitate identification of participants for clinical trials targeting amyloid beta (Abeta) accumulation, and aid in AD diagnostics. We examined the potential of plasma markers Abeta(1-42/1-40), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) to identify cerebral amyloidosis and/or disease severity. Methods: We included individuals with a positive (n = 176: 63 ± 7 years, 87 (49%) females) or negative (n = 76: 61 ± 9 years, 27 (36%) females) amyloid PET status, with syndrome diagnosis subjective cognitive decline (18 PET+, 25 PET-), mild cognitive impairment (26 PET+, 24 PET-), or AD-dementia (132 PET+). Plasma Abeta(1-42/1-40), GFAP, and NfL were measured by Simoa. We applied two-way ANOVA adjusted for age and sex to investigate the associations of the plasma markers with amyloid PET status and syndrome diagnosis; logistic regression analysis with Wald's backward selection to identify an optimal panel that identifies amyloid PET positivity; age, sex, and education-adjusted linear regression analysis to investigate associations between the plasma markers and neuropsychological test performance; and Spearman's correlation analysis to investigate associations between the plasma markers and medial temporal lobe atrophy (MTA). Results: Abeta(1-42/1-40) and GFAP independently associated with amyloid PET status (p = 0.009 and p < 0.001 respectively), and GFAP and NfL independently associated with syndrome diagnosis (p = 0.001 and p = 0.048 respectively). The optimal panel identifying a positive amyloid status included Abeta(1-42/1-40) and GFAP, alongside age and APOE (AUC = 88% (95% CI 83-93%), 82% sensitivity, 86% specificity), while excluding NfL and sex. GFAP and NfL robustly associated with cognitive performance on global cognition and all major cognitive domains (GFAP: range standardized β (sβ) = - 0.40 to - 0.26; NfL: range sβ = - 0.35 to - 0.18; all: p < 0.002), whereas Abeta(1-42/1-40) associated with global cognition, memory, attention, and executive functioning (range sβ = 0.22 - 0.11; all: p < 0.05) but not language. GFAP and NfL showed moderate positive correlations with MTA (both: Spearman's rho> 0.33, p < 0.001). Abeta(1-42/1-40) showed a moderate negative correlation with MTA (Spearman's rho = - 0.24, p = 0.001). Discussion and conclusions: Combination of plasma Abeta(1-42/1-40) and GFAP provides a valuable tool for the identification of amyloid PET status. Furthermore, plasma GFAP and NfL associate with various disease severity measures suggesting potential for disease monitoring.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)

Nyckelord

Alzheimer's continuum
Amyloid pathology
Blood-based biomarkers
Plasma amyloid beta
Plasma GFAP

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