Evidence map›Paper›PMID 35734478›Full record

ArticleFrontiers in neurology2022

Technical Performance Evaluation of Olink Proximity Extension Assay for Blood-Based Biomarker Discovery in Longitudinal Studies of Alzheimer's Disease.

Becky C Carlyle, Robert R Kitchen, Zoe Mattingly, Amanda M Celia, Bianca A Trombetta, Sudeshna Das, Bradley T Hyman, Pia Kivisäkk, Steven E Arnold

Open access · goldAbstract read
In one paragraph

Article in Frontiers in neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
5.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 51 citations in OpenAlex.

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  14. Targeting dysregulated CB1 receptors in a Down syndrome mouse model improves neurological outcomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Becky C CarlyleDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Robert R KitchenCardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Zoe MattinglyDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Amanda M CeliaDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Bianca A TrombettaDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Sudeshna DasDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Bradley T HymanDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Pia KivisäkkDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Steven E ArnoldDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Massachusetts General Hospital · USHarvard University · US

Funding

EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI STEVEN E ARNOLD · 2019 to 2026
$36.5M
The Massachusetts and Yale ADRC Collaborative Proteomic Biofluid Biomarker Discovery ProgramR01AG062306 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI ARNOLD, STEVEN E, CARLYLE, BECKY CATHERINE · 2018 to 2022
$3.5M
GBA pathway markers for Lewy body dementiasU01NS100603 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI SCHERZER, CLEMENS R · 2016 to 2020
$2.9M
Biomarkers for early intervention in Parkinson diseaseU01NS082157 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI SCHERZER, CLEMENS R · 2012 to 2016
$2.5M
Targeted Proteomics of Resilient Cognition in AgingR01AG039478 · NIA · UNIVERSITY OF PENNSYLVANIA · PI ARNOLD, STEVEN E · 2011 to 2015
$2.5M
NIA NIH HHS P30 AG062421NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG039478NIA NIH HHS R01 AG062306NINDS NIH HHS U01 NS082157NINDS NIH HHS U01 NS100603
6 · The paper itself

Abstract

The core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers; amyloid-β (Aß), total tau (t-tau), and phosphorylated tau (p-tau181), are strong indicators of the presence of AD pathology, but do not correlate well with disease progression, and can be difficult to implement in longitudinal studies where repeat biofluid sampling is required. As a result, blood-based biomarkers are increasingly being sought as alternatives. In this study, we aimed to evaluate a promising blood biomarker discovery technology, Olink Proximity Extension Assays for technical reproducibility characteristics in order to highlight the advantages and disadvantages of using this technology in biomarker discovery in AD. We evaluated the performance of five Olink Proteomic multiplex proximity extension assays (PEA) in plasma samples. Three technical control samples included on each plate allowed calculation of technical variability. Biotemporal stability was measured in three sequential annual samples from 54 individuals with and without AD. Coefficients of variation (CVs), analysis of variance (ANOVA), and variance component analyses were used to quantify technical and individual variation over time. We show that overall, Olink assays are technically robust, with the largest experimental variation stemming from biological differences between individuals for most analytes. As a powerful illustration of one of the potential pitfalls of using a multi-plexed technology for discovery, we performed power calculations using the baseline samples to demonstrate the size of study required to overcome the need for multiple test correction with this technology. We show that the power of moderate effect size proteins was strongly reduced, and as a result investigators should strongly consider pooling resources to perform larger studies using this multiplexed technique where possible.

Indexed as

Alzheimer's diseasebiomarkerbiotemporal stabilityneurodegenerationOlinkplasma

Identifiers

PMID35734478
PMCPMC9207419
OpenAlexW4281783629

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.