Confounding factors of Alzheimer's disease plasma biomarkers and their impact on clinical performance
Pichet Binette, Alexa LU ; Janelidze, Shorena LU ; Cullen, Nicholas LU ; Dage, Jeffrey L. ; Bateman, Randall J. ; Zetterberg, Henrik LU ; Blennow, Kaj LU ; Stomrud, Erik LU
; Mattsson-Carlgren, Niklas
LU
and Hansson, Oskar
LU
(2023)
In Alzheimer's and Dementia
19(4).
p.1403-1414
- 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... (More)
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.
(Less)
- author
- Pichet Binette, Alexa
LU
; Janelidze, Shorena
LU
; Cullen, Nicholas
LU
; Dage, Jeffrey L.
; Bateman, Randall J.
; Zetterberg, Henrik
LU
; Blennow, Kaj
LU
; Stomrud, Erik
LU
; Mattsson-Carlgren, Niklas
LU
and Hansson, Oskar
LU
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- amyloid, cerebrospinal fluid, dementia, glial fibrillary acidic protein, neurofilament light, p-tau
- in
- Alzheimer's and Dementia
- volume
- 19
- issue
- 4
- pages
- 1403 - 1414
- publisher
- Wiley
- external identifiers
-
- pmid:36152307
- scopus:85138752020
- ISSN
- 1552-5260
- DOI
- 10.1002/alz.12787
- language
- English
- LU publication?
- yes
- id
- ae63d221-eca9-462e-8632-2ca02ffe494f
- date added to LUP
- 2022-12-19 15:09:28
- date last changed
- 2025-01-27 15:19:15
@article{ae63d221-eca9-462e-8632-2ca02ffe494f,
abstract = {{<p>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.</p>}},
author = {{Pichet Binette, Alexa and Janelidze, Shorena and Cullen, Nicholas and Dage, Jeffrey L. and Bateman, Randall J. and Zetterberg, Henrik and Blennow, Kaj and Stomrud, Erik and Mattsson-Carlgren, Niklas and Hansson, Oskar}},
issn = {{1552-5260}},
keywords = {{amyloid; cerebrospinal fluid; dementia; glial fibrillary acidic protein; neurofilament light; p-tau}},
language = {{eng}},
number = {{4}},
pages = {{1403--1414}},
publisher = {{Wiley}},
series = {{Alzheimer's and Dementia}},
title = {{Confounding factors of Alzheimer's disease plasma biomarkers and their impact on clinical performance}},
url = {{http://dx.doi.org/10.1002/alz.12787}},
doi = {{10.1002/alz.12787}},
volume = {{19}},
year = {{2023}},
}