Evidence map›Paper›PMID 35195758›Full record

ArticleActa neuropathologica2022

Plasma biomarkers for Alzheimer's Disease in relation to neuropathology and cognitive change.

Denis S Smirnov, Nicholas J Ashton, Kaj Blennow, Henrik Zetterberg, Joel Simrén, Juan Lantero-Rodriguez, Thomas K Karikari, Annie Hiniker, Robert A Rissman, David P Salmon and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Acta neuropathologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
145citing papers in PubMed, 1 pooled it
32.1field-weighted citation impact, top 1% 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

145 citing papers in PubMed, 1 synthesis or guideline pooled it, 223 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
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  7. Prospective study on physical activity and Alzheimer's disease-related biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  17. A novel eye-tracking digital marker outperforms plasma biomarkers in detecting cognitive impairment.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  18. Article
  19. Article
  20. Article

85 more citing papers are in PubMed but not listed here.

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

11 authors at 5 institutions in 3 countries.

Denis S Smirnov *University of California, San Diego and Shiley-Marcos Alzheimer's Disease Research Center, La Jolla, CA, USA.
Nicholas J Ashton *Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Kaj BlennowInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Henrik ZetterbergInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Joel SimrénInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Juan Lantero-RodriguezInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Thomas K KarikariInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Annie HinikerUniversity of California, San Diego and Shiley-Marcos Alzheimer's Disease Research Center, La Jolla, CA, USA.
Robert A RissmanUniversity of California, San Diego and Shiley-Marcos Alzheimer's Disease Research Center, La Jolla, CA, USA.
David P SalmonUniversity of California, San Diego and Shiley-Marcos Alzheimer's Disease Research Center, La Jolla, CA, USA.
Douglas GalaskoUniversity of California, San Diego and Shiley-Marcos Alzheimer's Disease Research Center, La Jolla, CA, USA. dgalasko@ucsd.edu.ORCID 0000-0001-6195-3241
University of California San Diego · USSahlgrenska University Hospital · SEKing's College London · GBUniversity of Gothenburg · SEUniversity of Pittsburgh · US

Funding

UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JAMES B BREWER · 2019 to 2026
$34.9M
USCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI, ARTHUR W TOGA · 2020 to 2026
$27.8M
Chemical-Genetic Approaches to Define Lrrk2 Kinase Function in Parkinson DiseaseK08NS090633 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HINIKER, ANNIE E · 2014 to 2018
$1.1M
Repetition Priming Deficits and Locus Coeruleus Dysfunction in Alzheimer's DiseaseF30AG063440 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SMIRNOV, DENIS · 2019 to 2022
$179k
NIA NIH HHS F30 AG063440NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG066530NINDS NIH HHS K08 NS090633
6 · The paper itself

Abstract

Plasma biomarkers related to amyloid, tau, and neurodegeneration (ATN) show great promise for identifying these pathological features of Alzheimer's Disease (AD) as shown by recent clinical studies and selected autopsy studies. We have evaluated ATN plasma biomarkers in a series of 312 well-characterized longitudinally followed research subjects with plasma available within 5 years or less before autopsy and examined these biomarkers in relation to a spectrum of AD and related pathologies. Plasma Aβ42, Aβ40, total Tau, P-tau181, P-tau231 and neurofilament light (NfL) were measured using Single molecule array (Simoa) assays. Neuropathological findings were assessed using standard research protocols. Comparing plasma biomarkers with pathology diagnoses and ratings, we found that P-tau181 (AUC = 0.856) and P-tau231 (AUC = 0.773) showed the strongest overall sensitivity and specificity for AD neuropathological change (ADNC). Plasma P-tau231 showed increases at earlier ADNC stages than other biomarkers. Plasma Aβ42/40 was decreased in relation to amyloid and AD pathology, with modest diagnostic accuracy (AUC = 0.601). NfL was increased in non-AD cases and in a subset of those with ADNC. Plasma biomarkers did not show changes in Lewy body disease (LBD), hippocampal sclerosis of aging (HS) or limbic-predominant age-related TDP-43 encephalopathy (LATE) unless ADNC was present. Higher levels of P-tau181, 231 and NfL predicted faster cognitive decline, as early as 10 years prior to autopsy, even among people with normal cognition or mild cognitive impairment. These results support plasma P-tau181 and 231 as diagnostic biomarkers related to ADNC that also can help to predict future cognitive decline, even in predementia stages. Although NfL was not consistently increased in plasma in AD and shows increases in several neurological disorders, it had utility to predict cognitive decline. Plasma Aβ42/40 as measured in this study was a relatively weak predictor of amyloid pathology, and different assay methods may be needed to improve on this. Additional plasma biomarkers are needed to detect the presence and impact of LBD and LATE pathology.

Indexed as

Alzheimer DiseaseCognitive DysfunctionLewy Body DiseaseAmyloid beta-PeptidesBiomarkersCognitionHumanstau ProteinsAmyloid beta-PeptidesBiomarkerstau ProteinsAlzheimer’s DiseaseBiomarkerDementiaNeuropathologyPlasma

Identifiers

PMID35195758
PMCPMC8960664
OpenAlexW4213423501

What OpenQuestion holds

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LicenceCC BY
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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.