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Alterations of gut microbiota in Down syndrome and their association with Alzheimer's disease

Pellegrini, C.; Ravaioli, F.; De Fanti, S.; Sala, C.; Rochat, M.; Pollarini, V.; Polischi, B.; Pasti, A.; Grasso, M.; Rambaldi, M.; Cardoni, F.; Grotteschi, N.; Caraci, F.; Cortelli, P.; Provini, F.; Lodi, R.; Morandi, L.; Parchi, P.; Pirazzoli, G. L.; Sambati, L.; Tonon, C.; Bacalini, M. G.

2026-04-04 microbiology
10.64898/2026.04.03.716276 bioRxiv
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Structured AbstractO_ST_ABSINTRODUCTIONC_ST_ABSAdults with Down syndrome (DS) have a higher risk of developing Alzheimers disease (AD). As gut microbiota (GM) alterations have been reported in AD, we investigated their association with cognitive decline and plasma AD biomarkers in DS. METHODSFecal and plasma samples were collected from 58 adults with DS (21-75 years) and 30 euploid controls (CTRL; 25-83 years). GM was profiled using 16S rRNA sequencing. Major Neurocognitive Disorder (NcD) was diagnosed according to DSM-5 criteria. Plasma levels of p-Tau181, NfL, and GFAP were measured using the Simoa platform. RESULTSCompared with CTRL, DS showed significant changes in UBA1819 and Intestinibacter genera, previously reported to be associated with mild cognitive impairment. Furthermore, DS with NcD were characterized by a reduced abundance of Roseburia genus, which was also negatively associated with plasma levels of AD biomarkers. CONCLUSIONAdults with DS display AD-associated changes in GM partially resembling those previously reported in euploid AD patients

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