Alzheimer’s Research & Therapy (Sep 2020)

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

  • Inge M. W. Verberk,
  • Elisabeth Thijssen,
  • Jannet Koelewijn,
  • Kimberley Mauroo,
  • Jeroen Vanbrabant,
  • Arno de Wilde,
  • Marissa D. Zwan,
  • Sander C. J. Verfaillie,
  • Rik Ossenkoppele,
  • Frederik Barkhof,
  • Bart N. M. van Berckel,
  • Philip Scheltens,
  • Wiesje M. van der Flier,
  • Erik Stoops,
  • Hugo M. Vanderstichele,
  • Charlotte E. Teunissen

DOI
https://doi.org/10.1186/s13195-020-00682-7
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 14

Abstract

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Abstract 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 0.33, 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.

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