TY - JOUR
T1 - Confounding factors of Alzheimer's disease plasma biomarkers and their impact on clinical performance
AU - Pichet Binette, Alexa
AU - Janelidze, Shorena
AU - Cullen, Nicholas
AU - Dage, Jeffrey L.
AU - Bateman, Randall J.
AU - Zetterberg, Henrik
AU - Blennow, Kaj
AU - Stomrud, Erik
AU - Mattsson-Carlgren, Niklas
AU - Hansson, Oskar
N1 - Publisher Copyright:
© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
KW - amyloid
KW - cerebrospinal fluid
KW - dementia
KW - glial fibrillary acidic protein
KW - neurofilament light
KW - p-tau
UR - http://www.scopus.com/inward/record.url?scp=85138752020&partnerID=8YFLogxK
U2 - 10.1002/alz.12787
DO - 10.1002/alz.12787
M3 - Article
C2 - 36152307
AN - SCOPUS:85138752020
SN - 1552-5260
VL - 19
SP - 1403
EP - 1414
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 4
ER -