Journal Article

FZJ-2026-04866

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Fecal Aβ and tau aggregates are elevated in cognitive impairment and reveal peripheral proteopathic alterations

Özdüzenciler, P. (First author)FZJ* ; Müller, L. ; Kara, E. ; Weber, M.-C. ; Pils, M. ; Rehn, F. ; Bannach, O. ; Fink, G. R.FZJ* ; Willbold, D. ; Barbe, M. T. ; Onur, O. A. ; Tamgüney, E. G. (Corresponding author)FZJ*

2026
BioMed Central London

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Please use a persistent id in citations: doi:10.1186/s13195-026-02188-0  doi:10.34734/FZJ-2026-04866

Abstract: AbstractBackground Aggregation of amyloid-β (Aβ) and tau is central to Alzheimer’s disease (AD) pathogenesis and formsthe basis of established cerebrospinal fluid (CSF) and imaging biomarkers. However, increasing evidence suggeststhat AD involves systemic processes beyond the central nervous system. We previously demonstrated the presenceof fecal Aβ aggregates. Here, we assessed the detectability of tau aggregates in human feces and examined thediagnostic value of combined fecal Aβ and tau quantification in cognitive impairment.Methods Using surface-based fluorescence intensity distribution analysis (sFIDA), a single-particle assay selective foraggregated species, we quantified fecal Aβ and tau aggregates in individuals with cognitive impairment (dementia,MCI, SCD) and cognitively normal controls. Associations with CSF biomarkers were assessed, and classificationperformance was evaluated using cross-validated logistic regression models.Results Tau aggregates were detectable in fecal samples. Both fecal Aβ and tau aggregate concentrations weresignificantly elevated in cognitively impaired individuals and remained independently associated with patientstatus after adjustment for age and sex. Fecal Aβ aggregates showed inverse associations with CSF tau biomarkers,particularly phosphorylated tau. In cross-validated models, fecal tau aggregates achieved stronger classificationperformance than fecal Aβ (AUC ~ 0.80 vs. ~ 0.68), and integration of fecal aggregates with demographic predictorsimproved discrimination to an AUC of 0.90.Conclusions Detection of fecal tau aggregates extends previous observations on fecal Aβ and supports the conceptthat stool-based aggregate measurements capture systemic aspects of proteopathic biology associated withcognitive impairment. These findings suggest that fecal aggregate quantification may provide a minimally invasivebiomarker approach that complements established CNS-based biomarkers and may be useful for patient stratificationand monitoring in neurodegenerative disease.Keywords Alzheimer’s disease, Amyloid-β aggregates, Tau aggregates, Fecal biomarkers, Non-invasive diagnostics,Gut-brain axis, sFIDA

Note: GT was supported by the Förderstiftung Dierichs and the Deutsche Alzheimer Gesellschaft e.V. Selbsthilfe Demenz (DalzG). OAO and GRF were supported by the Marga and Walter Boll Foundation.

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Contributing Institute(s):

1. Kognitive Neurowissenschaften (INM-3)
2. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5251 - Multilevel Brain Organization and Variability (POF4-525) (POF4-525)

Appears in the scientific report 2026

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