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Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly
Open accessAbstract
The pathway leading from amyloid-β deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1β, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-α]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n = 40, Amy+) and with no brain amyloidosis (n = 33, Amy-) and also in a group of controls (n = 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1β) compared with both controls and with Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of E. rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC = -9.6, p < 0.001 and FC = +12.8, p < 0.001, respectively) and to Amy- (FC = -7.7, p < 0.001 and FC = +7.4, p = 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1β, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho = 0.60, p < 0.001; rho = 0.57, p < 0.001; and rho = 0.30, p = 0.007, respectively) and a negative correlation with the anti-inflammatory E. rectale (rho = -0.48, p < 0.001; rho = -0.25, p = 0.024; rho = -0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation.
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“Pro-inflammatory microbial taxa have been linked to elevated amyloid burden and systemic inflammation in cognitively impaired individuals213.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [213]
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“Human studies comparing the composition of the GM of elderly participants suffering from cognitive impairment with healthy individuals indicate significant changes in GM composition. Specifically, there is an increase in pro-inflammatory taxa and a reduction in anti-inflammatory taxa (104–109).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [104]
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Metadata
- Authors
- Cattaneo, A., Cattane, N., Galluzzi, S., Provasi, S., Lopizzo, N., Festari, C., Ferrari, C., Guerra, U. P., Paghera, B., Muscio, C., Bianchetti, A., Volta, G. D., Turla, M., Cotelli, M. S., Gennuso, M., Prelle, A., Zanetti, O., Lussignoli, G., Mirabile, D., Bellandi, D., Gentile, S., Belotti, G., Villani, D., Harach, T., Bolmont, T., Padovani, A., Boccardi, M., & Frisoni, G. B.
- Affiliations
- King's College London (GB)
- Centro San Giovanni di Dio Fatebenefratelli (IT)
- Fondazione Poliambulanza Istituto Ospedaliero (IT)
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT)
- Azienda Ospedaliera Ospedale Maggiore (IT)
- Fondazione Europea Ricerca Biomedica (IT)
- University of Geneva (CH)
- Corresponding author
- Cattaneo, Annamaria
- ORCID
- Cattaneo, Annamaria
- Cattane, Nadia
- Galluzzi, Samantha
- Provasi, Stefania
- Lopizzo, Nicola
- Festari, Cristina
- Ferrari, Clarissa
- Guerra, Ugo Paolo
- Muscio, Cristina
- Bianchetti, Angelo
- Volta, Giorgio Dalla
- Cotelli, Maria Sofia
- Gennuso, Michele
- Prelle, Alessandro
- Zanetti, Orazio
- Gentile, Simona
- Bolmont, Tristan
- Padovani, Alessandro
- Boccardi, Marina
- Frisoni, Giovanni B.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 49
- Pages
- 60-68
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2508213551
- Cited by
- 1,382
- References
- 64
- Citations by year
- 2026: 117 · 2025: 174 · 2024: 223 · 2023: 178 · 2022: 221 · 2021: 180 · 2020: 113 · 2019: 86 · 2018: 58 · 2017: 31
- FWCI
- 30.33
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Licence
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- AVID-Radiopharmaceuticals
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- cerebral amyloidosis, Alzheimer's disease, gut microbiota, inflammatory cytokines, peripheral inflammation, cognitive impairment, older adults, Escherichia-Shigella, Eubacterium rectale, Faecalibacterium prausnitzii, Bacteroides fragilis, Pseudomonas aeruginosa, NLRP3 inflammasome, IL-1β, interleukin-6, CXCL2, IL-10, gut-brain axis, amyloid-beta
- MeSH terms
- Gastrointestinal Microbiome, Aged, Alzheimer Disease, Brain, Cognition Disorders, Female, Humans, Inflammation, Intestines, Male, Middle Aged, Cytokines, Amyloid beta-Peptides, Inflammation Mediators, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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