Confounding factors of Alzheimer's disease plasma biomarkers and their impact on clinical performance

Alzheimers Dement. 2023 Apr;19(4):1403-1414. doi: 10.1002/alz.12787. Epub 2022 Sep 24.

Abstract

Introduction: Plasma biomarkers will likely revolutionize the diagnostic work-up of Alzheimer's disease (AD) globally. Before widespread use, we need to determine if confounding factors affect the levels of these biomarkers, and their clinical utility.

Methods: Participants with plasma and CSF biomarkers, creatinine, body mass index (BMI), and medical history data were included (BioFINDER-1: n = 748, BioFINDER-2: n = 421). We measured beta-amyloid (Aβ42, Aβ40), phosphorylated tau (p-tau217, p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP).

Results: In both cohorts, creatinine and BMI were the main factors associated with NfL, GFAP, and to a lesser extent with p-tau. However, adjustment for BMI and creatinine had only minor effects in models predicting either the corresponding levels in CSF or subsequent development of dementia.

Discussion: Creatinine and BMI are related to certain plasma biomarkers levels, but they do not have clinically relevant confounding effects for the vast majority of individuals.

Highlights: Creatinine and body mass index (BMI) are related to certain plasma biomarker levels. Adjusting for creatinine and BMI has minor influence on plasma-cerebrospinal fluid (CSF) associations. Adjusting for creatinine and BMI has minor influence on prediction of dementia using plasma biomarkers.

Keywords: amyloid; cerebrospinal fluid; dementia; glial fibrillary acidic protein; neurofilament light; p-tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / cerebrospinal fluid
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Creatinine
  • Humans
  • tau Proteins / cerebrospinal fluid

Substances

  • Creatinine
  • tau Proteins
  • Amyloid beta-Peptides
  • Biomarkers