Evidence map›Paper›PMID 40494737›Full record

ArticleThe journal of prevention of Alzheimer's disease2025

Salivary levels of amyloid beta reflect brain amyloid beta burden in cognitively-normal older adults.

Alison R Bamford, Jenna N Adams, Soyun Kim, Lisa M Taylor, Nandita Tuteja, Liv C McMillan, Negin Sattari, Ivy Y Chen, Miranda G Chappel-Farley, Yuritza Escalante and 9 more

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Article in The journal of prevention of Alzheimer's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. 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

19 authors.

Alison R BamfordDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA; Institute for Interdisciplinary Salivary Bioscience Research, University of California Irvine, Irvine, CA, USA.
Jenna N AdamsDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA; Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA, USA.
Soyun KimDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA; Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA, USA.
Lisa M TaylorDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA; Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA, USA.
Nandita TutejaDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
Liv C McMillanDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA; Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA, USA.
Negin SattariDepartment of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA.
Ivy Y ChenDepartment of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA.
Miranda G Chappel-FarleyDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA; Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Yuritza EscalanteDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
Alyssa L LawrenceDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
Novelle J MezaDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
Destiny E BerishaDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA; Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA, USA.
Abhishek DaveDepartment of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA; Department of Neurology, School of Medicine, University of California Irvine, Irvine, CA, USA.
Rond MalhasDepartment of Neurology, School of Medicine, University of California Irvine, Irvine, CA, USA.
Mark MapstoneDepartment of Neurology, School of Medicine, University of California Irvine, Irvine, CA, USA.
Bryce A ManderCenter for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA, USA; Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA; Department of Cognitive Sciences, University of California Irvine Irvine, CA, USA.
Michael A YassaDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA; Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA, USA; Department of Cognitive Sciences, University of California Irvine Irvine, CA, USA.
Elizabeth A ThomasDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA; Institute for Interdisciplinary Salivary Bioscience Research, University of California Irvine, Irvine, CA, USA; Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA; Department of Neurosciences, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: eathoma1@uci.edu.

Funding

UC Irvine Alzheimer's Disease Research Center Induced Pluripotent Stem Cell CoreP50AG016573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI YASSA, MICHAEL A · 2000 to 2019
$37.0M
University of California Health Participation in the National COVID Cohort Collaborative (N3C)UL1TR001414 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M, VILAIN, ERIC J. · 2015 to 2023
$35.1M
Neuroimaging biomarkers for cognitive decline in elderly with amyloid pathologyR01AG053555 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Michael A Yassa · 2017 to 2026
$17.0M
Institute for Clinical and Translational ScienceUM1TR004927 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAN M COOPER, Eric J. Vilain · 2024 to 2026
$12.2M
Training Program in Learning and MemoryT32MH119049 · NIMH · UNIVERSITY OF CALIFORNIA-IRVINE · PI BRUCE L MCNAUGHTON, Manuella Yassa · 2019 to 2026
$1.4M
Relationships between local and global mechanisms of sleep apnea, Alzheimer's disease biomarkers, and memory impairment in cognitively asymptomatic older adultsK01AG068353 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI MANDER, BRYCE A. · 2020 to 2024
$636k
Circuit-specific tau burden and mechanisms of sleep-dependent memory processing in older adults at risk for Alzheimer’s diseaseR21AG079552 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI MANDER, BRYCE A., YASSA, MICHAEL A · 2022 to 2022
$432k
Cerebrovascular and neurophysiological mechanisms of sleep-dependent memory impairment in older adults at risk for Alzheimer's diseaseF31AG084308 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BERISHA, DESTINY · 2024 to 2025
$82k
NCATS NIH HHS UL1 TR001414NCATS NIH HHS UM1 TR004927NIA NIH HHS F31 AG084308NIA NIH HHS K01 AG068353NIA NIH HHS P50 AG016573NIA NIH HHS R01 AG053555NIA NIH HHS R21 AG079552NIMH NIH HHS T32 MH119049
6 · The paper itself

Abstract

backgroundAmyloid beta (Aβ) plaque burden, as measured by positron emission tomography (PET), is increasingly being used as a biomarker for Alzheimer's disease (AD) as well as a screening or monitoring tool for clinical trials with amyloid-lowering drugs. However, PET imaging is expensive, invasive and not widely available for all patients, necessitating alternative means to assess brain Aβ accumulation.

objectivesIn this study, we measured levels of Aβ42, Aβ40 and Aβ38 in saliva samples from cognitively unimpaired older adults (n=93; 61.7 % female; mean age = 70.1 ± 6.6 years) using the Mesoscale Discovery platform, carefully considering preanalytical variables, including timing of sample collection, blood contamination and sample concentration. We next determined the relationships between Aβ peptide levels and Aβ plaque burden within the brain, determined using 18F-florbetapir (FBP) PET.

resultsWe found that salivary levels of Aβ38 and Aβ42, but not Aβ40 nor the Aβ42/Aβ40, were significantly positively correlated with the global mean FBP standardized uptake value ratio (SUVR), before and after adjusting for age, sex and time of day of saliva sample collection (r=0.523/0.544, p=0.001/0.002 and r=0.316/0.32, p=0.031/0.044, for Aβ38 and Aβ42, respectively). Similar results were observed when Aβ values were analyzed as a ratio to the total protein levels in each sample and when tested in saliva samples that were collected during a restricted morning time window. Using composite regions which represent cortical regions vulnerable to Aβ accumulation in early, intermediate, and late stages of AD, we found that Aβ38 showed the most robust correlation with FBP SUVRs from early-accumulating brain regions (r=0.510; p<0.001). In contrast to the observed effects in saliva, plasma levels of Aβ42 measured from a subset of the participants showed a significant negative correlation to mean FBP SUVR. Using logistic regression analysis to determine whether any salivary Aβ species could predict brain Aβ burden, we found that salivary levels of Aβ38 in combination with age, sex, sample timing and APOE genotype could predict Aβ-PET positivity with an area under the curve = 0.950 (95 % confidence interval, 0.876-1.0; p<0.0001).

conclusionsOur findings suggest that salivary Aβ38 and/or Aβ42 could have relevance as a non-invasive, and more widely applicable biomarker, for utility in clinical studies on AD.

Indexed as

Amyloid beta-PeptidesBrainSalivaAgedAged, 80 and overAlzheimer DiseaseAniline CompoundsBiomarkersEthylene GlycolsFemaleHumansMaleMiddle AgedPeptide FragmentsPlaque, AmyloidPositron-Emission TomographyAmyloid beta-Peptidesamyloid beta-protein (1-40)Aniline CompoundsBiomarkersEthylene GlycolsflorbetapirPeptide FragmentsAlzheimer’s diseaseamyloid betabiomarkerneurodegenerationpositron emission tomographysaliva

Identifiers

PMID40494737
PMCPMC12252581

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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.