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Background: Human microbiota‐associated (HMA) murine models are developed by gavaging mice with human bacteria or stools and are increasingly used to study the relation between the human microbiota and disease. The aim of this study is to evaluate the effect of gut bacteria isolated from donors with or without Alzheimer's dementia on behavior in AD transgenic (Tg) mice. Method: Sixty female, one‐year old 3xTg mice (APPSWE, PS1M146V and TauP301L) received (1) antibiotic treatment for 14 days before first gavage, (2) stomach acid suppressant, (3) laxative immediately before the first gavage and, (4) microbiota transplantation or saline, once every 2 weeks for 2 months. The transplanted microbiota consisted of bacteria isolated from stools of donors pertaining to four different profiles: i) an amyloid positive AD patient,ii) an amyloid negative cognitively healthy subjects with or iii) without protective APOE genotype and, iv) a young healthy donor. As additional control, we included a group of mice that received bacteria isolated from stools of untreated 3xTg mice. Stools collection and behavioral assessment (open‐field test, Y‐maze test, radial maze test, elevated plus maze test) was performed before antibiotic treatment and at day 3, 30, 60 after the first gavage. All mice were sacrificed at day 60 for ex‐vivo assessments. Result: After 60 days from first gavage, bacteria from the AD patient (i) induced AD‐like behavior in 3xTg mice, including impaired general activity in the open‐field test and exacerbated anxiety in the elevated plus maze test, compared with mice that received saline or bacteria from untreated 3xTg mice. Interestingly, bacteria from donor resilient to AD pathology (donor of profile ii) induced better cognitive score to object recognition when transplanted to 3xTg mice. Conclusion: The microbiota of AD patients induced an AD‐like phenotype in 3xTg mice, and microbiota from patient resilient to AD pathology induced a better memory score. Brain and gut ex‐vivo assessments, 16S rRNA gene sequencing as well as behavioral longitudinal analysis are on‐going to evaluate the human microbiota transplantation efficiency and its effect on AD pathology and inflammation. [ABSTRACT FROM AUTHOR]

Early diagnosis of late‐onset Alzheimer's disease (AD) by peripheral biomarkers remains a challenge; many have been proposed, but none have been evaluated in a prospective manner. CLUSTERIN (CLU), a chaperone protein expressed in the brain and found in relatively high concentrations in plasma, is a promising candidate. CLU contributes to the elimination of β‐amyloid (Aβ), which is associated to neurofibrillary tangles and to the genetic risk for AD. We performed a longitudinal measurement of CLU in the brain and the plasma in 3xTgAD mice. Assessment of CLU was also conducted in 12‐month‐old TgF344‐AD rats. In humans, brain CLU was measured in non‐demented and in AD subjects. The plasma CLU was longitudinally measured in four cohorts defined as healthy controls that remained stable, healthy controls that presented a cognitive decline between the two measures, mild cognitive impairment (MCI) that presented a cognitive decline between the two measures and AD. A validation cohort composed of 19 MCI was used and plasma CLU was measured before and after conversion in AD. Increases in CLU were measured in the hippocampus of 3xTgAD and TgF344‐AD animals in the absence of plasmatic changes. CLU is heterogeneously expressed in the hippocampus in non‐demented individuals and increased in AD. In the plasma, two CLU levels were measured: low in controls and MCI, and high in AD. To validate that the elevation in CLU is associated with conversion to AD, a replication study showed, in a second group MCI patients converting to AD in the follow‐up that CLU levels increased in 16/19 individuals. The increase in brain CLU occurs in AD models as in humans, and seems to precede plasma variations, which could make it an AD therapeutic target. Plasma CLU seems to be a promising marker of cognitive decline, and its association with AD may be a useful complementary diagnostic tool. [ABSTRACT FROM AUTHOR]