Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease

Pratishtha Chatterjee, Steve Pedrini, Nicholas J. Ashton, Michelle Tegg, Kathryn Goozee, Abhay K. Singh, Thomas K. Karikari, Joel Simrén, Eugeen Vanmechelen, Nicola J. Armstrong, Eugene Hone, Prita R. Asih, Kevin Taddei, Vincent Dore, Victor L. Villemagne, Hamid R. Sohrabi, Henrik Zetterberg, Colin L. Masters, Kaj Blennow, Ralph N. Martins*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)


Introduction: This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t-tau), phosphorylated tau (p-tau181 and p-tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD). Methods: Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ−) or presence (Aβ+) of brain amyloidosis. Results: Plasma GFAP, t-tau, p-tau181, and p-tau231 concentrations were higher in Aβ+ CU compared with Aβ− CU cross-sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aβ+ and Aβ− CU; however, no statistically significant differences were observed between the AUCs of GFAP, p-tau181, and p-tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t-tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene (APOE) ε4 status with GFAP was observed to have a higher AUC (>90%) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p-tau181 in Aβ+ CU and increased NFL in Aβ− CU, over a 12-month duration. GFAP, p-tau181, p-tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippocampal volume. Discussion: These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p-tau for preclinical AD.
Original languageEnglish
Pages (from-to)1141-1154
Number of pages14
JournalAlzheimer's and Dementia
Issue number6
Early online date8 Sept 2021
Publication statusPublished - Jun 2022


  • Alzheimer's disease
  • amyloid beta
  • blood biomarkers
  • brain amyloid beta
  • diagnosis
  • glial fibrillary acidic protein
  • longitudinal monitoring
  • neurofilament light
  • p-tau181
  • p-tau231
  • preclinical Alzheimer's disease
  • single molecule array
  • tau


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