Evidence map›Paper›PMID 37574735›Full record

ArticleJournal of Alzheimer's disease : JAD2023

Pre-Analytical Variables Influencing Stability of Blood-Based Biomarkers of Neuropathology.

Daniel Panikkar, Sithara Vivek, Eileen Crimmins, Jessica Faul, Kenneth M Langa, Bharat Thyagarajan

Open access · greenAbstract read
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 2 pooled it
5.2field-weighted citation impact, top 4% 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

21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Diagnostic performance of salivary markers of Alzheimer's disease: A systematic review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Pooled it
  3. Distinct ocular microvascular alterations in Alzheimer's disease and cerebral small vessel disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  4. Review
  5. Article
  6. Comparative analyses of Alzheimer's disease blood biomarkers and cognitive domains.medRxiv : the preprint server for health sciences · 2026
    Article
  7. Article
  8. Article
  9. Substituting blood-based biomarkers for imaging measures in Alzheimer's disease studies: implications for sample size and bias.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026
    Article
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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

6 authors at 3 institutions in 1 country.

Daniel PanikkarDepartment of Neuroscience, University of Minnesota, Minneapolis, MN, USA.
Sithara VivekDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Eileen CrimminsDavis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Jessica FaulInstitute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, USA.
Kenneth M LangaInstitute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, USA.
Bharat ThyagarajanDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
University of Minnesota · USUniversity of Michigan · USUniversity of Southern California · US

Funding

HRS Yrs29-34: Y33 SSA CoFundingU01AG009740 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jessica Faul, KENNETH M LANGA · 1990 to 2026
$555.8M
USC/UCLA Center on Biodemography &Population HealthP30AG017265 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JENNIFER A AILSHIRE · 1999 to 2026
$17.9M
Health and Retirement Study: Harmonized Cognitive Assessment Protocol (HCAP)U01AG058499 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LANGA, KENNETH M · 2018 to 2023
$8.3M
Biological Underpinnings of Socioeconomic Differentials in Health and MortalityR01AG060110 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CRIMMINS, EILEEN M · 2018 to 2022
$2.6M
Biological Risk Underlying Education Health DifferencesR01AG023347 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CRIMMINS, EILEEN M. · 2003 to 2006
$1.4M
NIA NIH HHS P30 AG017265NIA NIH HHS R01 AG023347NIA NIH HHS R01 AG060110NIA NIH HHS U01 AG058499
6 · The paper itself

Abstract

backgroundSample collection and preanalytical protocols may significantly impact the results of large-scale epidemiological studies incorporating blood-based biomarkers of neuropathology.

objectiveTo evaluate the stability and assay variability of several blood-based biomarkers of neuropathology for common preanalytical conditions.

methodsWe collected serum and plasma samples from 41 participants and evaluated the effect of processing delay of up to 72 h when stored at 4∘C, three freeze-thaw cycles, and a combination of 48-h processing delay when stored at 4∘C and three freeze-thaw cycles on biomarker stability. Using the Simoa assay (Quanterix Inc.), we measured amyloid-β 40 (Aβ40), amyloid-β 42 (Aβ42), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau 181 (p-tau-181).

resultsWe found that Aβ40 and Aβ42 levels significantly decreased after a 24-h processing delay in both plasma and serum samples, and a single freeze-thaw cycle (p < 0.0001). Nevertheless, serum Aβ42/40 ratio remained stable with a processing delay up to 48 h while plasma Aβ42/40 ratio showed only small but significant increase with a delay up to 72 h. Both plasma and serum GFAP and NfL levels were only modestly affected by processing delay and freeze-thaw cycles. Plasma p-tau-181 levels notably increased with a 24-, 48-, and 72-h processing delay, but remained stable in serum. Intra-individual variation over two weeks was minimal for all biomarkers and their levels were substantially lower in serum when compared with plasma.

conclusionThese results suggest that standardizing preanalytical variables will allow robust measurements of biomarkers of neuropathology in population studies.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesBiomarkersHumansPlasmaSerumtau ProteinsAmyloid beta-PeptidesBiomarkerstau ProteinsAlzheimer’s diseaseamyloid-βblood-based biomarkerspre-analytical variablesSimoa assaystability

Identifiers

PMID37574735
PMCPMC11520930
OpenAlexW4385666316

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.