Evidence map›Paper›PMID 37254223›Full record

ArticleAlzheimer's research & therapy2023

A peripheral signature of Alzheimer's disease featuring microbiota-gut-brain axis markers.

Moira Marizzoni, Peppino Mirabelli, Elisa Mombelli, Luigi Coppola, Cristina Festari, Nicola Lopizzo, Delia Luongo, Monica Mazzelli, Daniele Naviglio, Jean-Louis Blouin and 5 more

Open access · goldAbstract read
In one paragraph

Article in Alzheimer's research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
16.3field-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

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.

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3 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

15 authors at 7 institutions in 2 countries.

Moira MarizzoniLaboratory of Biological Psychiatry, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, Italy. mmarizzoni@fatebenefratelli.eu.
Peppino MirabelliIRCCS SYNLAB SDN, Naples, Italy.
Elisa MombelliLaboratory of Biological Psychiatry, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, Italy.
Luigi CoppolaIRCCS SYNLAB SDN, Naples, Italy.
Cristina FestariLaboratory of Neuroimaging and Alzheimer's Epidemiology, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, Italy.
Nicola LopizzoLaboratory of Biological Psychiatry, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, Italy.
Delia LuongoIstituto Di Biostrutture E Bioimmagini (I.B.B.) - CNR, Naples, Italy.
Monica MazzelliLaboratory of Biological Psychiatry, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, Italy.
Daniele NaviglioDip.to Di Scienze Chimiche, Università Degli Studi Di Napoli - Federico II, Naples, Italy.
Jean-Louis BlouinGenetic Medicine Division, University Hospitals and University of Geneva, Geneva, Switzerland.
Marc AbramowiczGenetic Medicine Division, University Hospitals and University of Geneva, Geneva, Switzerland.
Marco SalvatoreIRCCS SYNLAB SDN, Naples, Italy.
Michela PievaniLaboratory of Neuroimaging and Alzheimer's Epidemiology, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, Italy.
Annamaria CattaneoLaboratory of Biological Psychiatry, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, Italy.
Giovanni B FrisoniMemory Clinic and LANVIE - Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland.
Centro San Giovanni di Dio Fatebenefratelli · ITIstituti di Ricovero e Cura a Carattere Scientifico · ITUniversity Hospital of Geneva · CHInstitute of Biostructure and Bioimaging · ITUniversity of Geneva · CHUniversity of Milan · ITUniversity of Naples Federico II · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIncreasing evidence links the gut microbiota (GM) to Alzheimer's disease (AD) but the mechanisms through which gut bacteria influence the brain are still unclear. This study tests the hypothesis that GM and mediators of the microbiota-gut-brain axis (MGBA) are associated with the amyloid cascade in sporadic AD.

methodsWe included 34 patients with cognitive impairment due to AD (CI-AD), 37 patients with cognitive impairment not due to AD (CI-NAD), and 13 cognitively unimpaired persons (CU). We studied the following systems: (1) fecal GM, with 16S rRNA sequencing; (2) a panel of putative MGBA mediators in the blood including immune and endothelial markers as bacterial products (i.e., lipopolysaccharide, LPS), cell adhesion molecules (CAMs) indicative of endothelial dysfunction (VCAM-1, PECAM-1), vascular changes (P-, E-Selectin), and upregulated after infections (NCAM, ICAM-1), as well as pro- (IL1β, IL6, TNFα, IL18) and anti- (IL10) inflammatory cytokines; (3) the amyloid cascade with amyloid PET, plasma phosphorylated tau (pTau-181, for tau pathology), neurofilament light chain (NfL, for neurodegeneration), and global cognition measured using MMSE and ADAScog. We performed 3-group comparisons of markers in the 3 systems and calculated correlation matrices for the pooled group of CI-AD and CU as well as CI-NAD and CU. Patterns of associations based on Spearman's rho were used to validate the study hypothesis.

resultsCI-AD were characterized by (1) higher abundance of Clostridia_UCG-014 and decreased abundance of Moryella and Blautia (p < .04); (2) elevated levels of LPS (p < .03), upregulation of CAMs, Il1β, IL6, and TNFα, and downregulation of IL10 (p < .05); (3) increased brain amyloid, plasma pTau-181, and NfL (p < 0.004) compared with the other groups. CI-NAD showed (1) higher abundance of [Eubacterium] coprostanoligenes group and Collinsella and decreased abundance of Lachnospiraceae_ND3007_group, [Ruminococcus]_gnavus_group and Oscillibacter (p < .03); (2) upregulation of PECAM-1 and TNFα (p < .03); (4) increased plasma levels of NfL (p < .02) compared with CU. Different GM genera were associated with immune and endothelial markers in both CI-NAD and CI-AD but these mediators were widely related to amyloid cascade markers only in CI-AD.

conclusionsSpecific bacterial genera are associated with immune and endothelial MGBA mediators, and these are associated with amyloid cascade markers in sporadic AD. The physiological mechanisms linking the GM to the amyloid cascade should be further investigated to elucidate their potential therapeutic implications.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesBiomarkersBrain-Gut AxisHumansInterleukin-10Interleukin-6LipopolysaccharidesMitoguazoneNADPlatelet Endothelial Cell Adhesion Molecule-1RNA, Ribosomal, 16STumor Necrosis Factor-alphaAmyloid beta-PeptidesBiomarkersInterleukin-10Interleukin-6Lipopolysaccharidesmethylglyoxal bis(3-aminopropylamidinohydrazone)MitoguazoneNADPlatelet Endothelial Cell Adhesion Molecule-1RNA, Ribosomal, 16STumor Necrosis Factor-alphaAlzheimer’s diseaseCognitive impairmentEndothelial dysfunctionGut microbiotaLipopolysaccharideMicrobiota-gut-brain axis

Identifiers

PMID37254223
PMCPMC10230724
OpenAlexW4378781690

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LicenceCC BY
Read underepoch 390

Registered trials

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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.