Proliferation and activation of microglia in the brain, concentrated around amyloid plaques, is a prominent feature of Alzheimer’s disease (AD). Human genetics data point to a key role for microglia in the pathogenesis of AD. The majority of risk genes for AD are highly expressed (and many are selectively expressed) by microglia in the brain. There is mounting evidence that microglia protect against the incidence of AD, as impaired microglial activities and altered microglial responses to &bgr;-amyloid are associated with increased AD risk. On the other hand, there is also abundant evidence that activated microglia can be harmful to neurons. Microglia can mediate synapse loss by engulfment of synapses, likely via a complement-dependent mechanism; they can also exacerbate tau pathology and secrete inflammatory factors that can injure neurons directly or via activation of neurotoxic astrocytes. Gene expression profiles indicate multiple states of microglial activation in neurodegenerative disease settings, which might explain the disparate roles of microglia in the development and progression of AD pathology.
Shakib Khan, Fariba Dambandkhameneh, Nazim Shaikh
et al.
Abstract Whole–slide image (WSI) analysis requires integrating fine-grained spatial structure with long-range tissue context. This work introduces SlideMamba, a hybrid framework that performs embedding-level fusion of a graph neural network (capturing local topology) and a Mamba state-space branch (modeling global context) via entropy-based confidence weighting. The adaptive fusion emphasizes the branch with lower predictive entropy, providing a principled mechanism to combine complementary feature streams and improving multi-scale representation learning. Effectiveness is demonstrated on two clinically relevant tasks with class imbalance: (i) mutation/fusion prediction from the OAK clinical trial WSIs (40 $$\times$$ ), where SlideMamba attains PRAUC $$0.740 \pm 0.033$$ , exceeding fixed-fusion (GAT-Mamba $$0.632 \pm 0.015$$ ) and single-branch baselines (Mamba $$0.630 \pm 0.015$$ , SlideGraph+ $$0.730 \pm 0.026$$ , MIL $$0.502 \pm 0.039$$ , TransMIL $$0.390 \pm 0.016$$ ); and (ii) LUAD vs. LUSC classification on an independent proprietary cohort (20 $$\times$$ ), where SlideMamba achieves PRAUC of $$0.969 \pm 0.015$$ , outperforming MIL (0.946 ± 0.037), TransMIL (0.929 ± 0.033), SlideGraph+ (0.945 ± 0.025), GAT-Mamba (0.935 ± 0.011), Mamba (0.962 ± 0.012). Beyond performance gains, the inclusion of the Mamba backbone ensures computational efficiency by avoiding the quadratic complexity of standard attention mechanisms. Furthermore, the adaptive fusion weights provide inherent interpretability, offering clinicians insight into whether local cellular graphs or global tissue architecture drove the final prediction. These attributes suggest SlideMamba offers a clinically feasible path toward spatially-resolved, precision computational pathology.
BackgroundMetaplastic carcinoma of the breast with mesenchymal differentiation (MCMD) is a type of metaplastic breast carcinoma (MpBC) that is very rare and aggressive. The present case provides valuable information for clinicians on this MpBC.Case presentationA 41-year-old woman visited our hospital for a palpable painless mass in the left breast. Core needle biopsy (CNB) was performed, and the pathological result was infiltrating ductal carcinoma. Epirubicin (100 mg/m2) + cyclophosphamide (600 mg/m2) for four cycles was given. Color Doppler ultrasound examination indicated no obvious change in the size of the left breast mass. We changed to paclitaxel (175 mg/m2) for two cycles. Re-examination on April 26, 2018 with color Doppler ultrasound indicated that the tumor diameter increased to 8.39 cm × 8.07 cm × 6.19 cm. Radical resection of the left breast carcinoma was performed on June 04, 2018. The postoperative pathological results showed that the left breast tumor was composed of carcinoma and sarcoma components, without nerves and vascular invasion. The immunohistochemistry results were as follows: ER: (−), PR: (−), HER2: (−), CK5/6 (+), CK7: (+), E-cadherin (+), Ki67: 40% (+), P120: (+), P53 diffuse +, P63: (+), and S100 partially positive, GATA-3: (+). Four cycles of vinorelbine (25 mg/m2) + cisplatin (40 mg/m2) were performed after the operation. Enhanced CT indicated a 6.0 cm × 4.6 cm mass in the liver on January 1, 2019 through regular review, and liver lobectomy confirmed that metastasis originated from sarcoma components, together with bone and cartilage differentiation. The immunohistochemistry results indicated the following: ER (−), PR (−), GATA-3 (−), CD34 (+), P63 (−), CK8 (−), P40: (−), and vimentin: (+). The patient received oral anlotinib 12 mg once a day, with 2 weeks on/1 week off for eight cycles. The patient survived and showed no signs of recurrence at the follow-up visit.ConclusionThis case indicated that CNB may not always give an accurate diagnosis for MCMD. Neoadjuvant chemotherapy with epirubicin, cyclophosphamide, or paclitaxel for MCMD may not be effective for patients showing no sensitivity to these drugs. In addition, regular postoperative follow-up plays an important role in the early detection of remote metastasis, and timely surgical excision of a single metastatic lesion in the liver can lead to long-term progression-free survival (PFS).
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Abstract Kidney renal clear cell carcinoma (KIRC) is a highly aggressive malignant tumor, and its occurrence and progression are influenced by tumor microenvironment (TME). CD159A, a natural killer (NK) cell inhibitory receptor, has emerged as a critical immune checkpoint in TME. We conducted a comprehensive multi-omics analysis of CD159A expression, prognostic significance, and functional enrichment in KIRC. Additionally, quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were employed to perform CD159A expression in the Xiangya KIRC validation cohort. Furthermore, in vitro experiments were evaluated through cell proliferation, colony formation, and flow cytometry (FC) analysis of apoptosis in KIRC cell lines. Our study found that CD159A expression was significantly upregulated in KIRC tissues compared to normal tissues, as confirmed by TCGA data and the Xiangya KIRC validation cohort. In machine learning analyses, the biological significance of the regulatory network risk factors of the CD159A-HLA-E pathway is immunosuppressive receptors or abnormal antigen presentation that may promote immune escape. Elevated CD159A levels were observed in NK cells and CD8+ T cells infiltrating KIRC by single-cell RNA sequencing analysis. A positive correlation between CD159A and NK/CD8+ T cell infiltration was observed, and higher CD159A expression in KIRC patients receiving anti-PD-1/PD-L1 immunotherapy was associated with improved outcomes. In vitro experiments demonstrated that silencing CD159A significantly suppressed proliferation, colony formation and induced apoptosis in KIRC cells. Our research highlights the critical role of CD159A as a key immune checkpoint in KIRC progression and immune evasion, suggesting its potential as a prognostic and immunotherapy biomarker.
Tharani Priya Thirumoorthy, Jobin John Jacob, Aravind Velmurugan
et al.
ABSTRACT The emergence and spread of Salmonella Typhi (S. Typhi) resistant to third-generation cephalosporins is a serious global health concern. In this study, we genomically characterized 142 cephalosporin-resistant S. Typhi strains isolated from India. Comparative genome analysis revealed the emergence of a new clone of ceftriaxone-resistant S. Typhi harboring three plasmids of the incompatibility groups IncFIB(K), IncX1, and IncFIB(pHCM2). Among these, the IncFIB(K) plasmid confers resistance to third-generation cephalosporins through the blaCTX-M-15 gene, along with other resistance determinants such as aph(3"), aph(6'), sul2, dfrA14, qnrS, and tet(A). Phylogenetic analysis showed that the isolates from Gujarat (n = 140/142) belong to a distinct subclade (genotype 4.3.1.2.2) within genotype 4.3.1.2 (H58 lineage II). Single nucleotide polymorphism-based phylogenetic analysis of the core genes in IncFIB(K) suggested a close relatedness of the plasmid backbone to that of IncFIB(K) from other Enterobacteriales, indicating that H58 lineage II possesses the capability to acquire MDR plasmids from these organisms. This could indicate the potential onset of a new wave of ceftriaxone-resistant S. Typhi in India. The implementation of control measures—such as vaccination and improved water, sanitation, and hygiene systems—is crucial in areas where MDR or extensively drug-resistant S. Typhi strains are prevalent to curb the spread and impact of these resistant strains.IMPORTANCETyphoid fever remains a global health concern, especially in areas lacking sanitation and clean water. The rise of drug-resistant strains complicates treatment, increasing illness, death, and healthcare expenses. Travel facilitates the spread of these strains worldwide. Multidrug-resistant and extensively drug-resistant (XDR) strains, including those resistant to first-line antibiotics and fluoroquinolones, pose significant challenges. Azithromycin and third-generation cephalosporins are now preferred treatments. Recently, XDR typhoid emerged in Pakistan, resistant even to third-generation cephalosporins. India also faces challenges, with sporadic cases initially declining but now re-emerging. New strains in India show resistance to third-generation cephalosporins due to plasmid acquisition from other bacteria, particularly blaCTX-M-carrying IncFIB(K). Due to the ongoing nature of this outbreak, the data from this study deserve further consideration in order to control its spread in India.
Farhad Rezazadeh, Shirin Aali, Fariborz Imani
et al.
<i>Background and Objectives:</i> Chronic low back pain (CLBP) is associated with altered neuromuscular control. Dynamic Neuromuscular Stabilization (DNS) targets core–limb coordination; however, its specific impact on lower-limb electromyographic (EMG) activity during gait remains unclear. <i>Materials and Methods:</i> Fifty-five young adults with non-specific CLBP (pain ≥ 3 months with no identifiable specific pathology) completed the trial (overall mean age 23.7 ± 1.3 years). Participants were randomized to an 8-week DNS program or a control. Pre-/Post-intervention surface EMG during gait and clinical outcomes (VAS, ODI) were assessed. <i>Results:</i> Compared with control, DNS showed lower adjusted Post-test VAS (3.08 ± 0.25 vs. 6.13 ± 0.24; <i>ηp</i><sup>2</sup> = 0.596) and ODI (15.73 ± 1.55% vs. 34.36 ± 1.52%; <i>ηp</i><sup>2</sup> = 0.579). Directionally, DNS was associated with phase-specific EMG modulation: tibialis anterior during mid-stance was lower (<i>ηp</i><sup>2</sup> = 0.137), rectus femoris during push-off was lower (<i>ηp</i><sup>2</sup> = 0.119), biceps femoris during push-off was lower (<i>ηp</i><sup>2</sup> = 0.168), and vastus medialis at heel-strike was higher (<i>ηp</i><sup>2</sup> = 0.077) relative to control. Other muscle–phase pairs showed no adjusted between-group differences. <i>Conclusions:</i> An 8-week DNS program was associated with clinically meaningful reductions in pain and disability and with phase-specific changes in lower-limb EMG during gait. These findings support DNS as a promising rehabilitation option for young adults with CLBP; confirmation in larger trials with active comparators is warranted.
Catherine Krus, Ian Zander, Tyler J. Sherman
et al.
Bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) are two viruses belonging to the genus Orbivirus that are transmitted via insect vector, the Culicoides biting midge, causing disease in domestic and wild ruminants. These infections can lead to significant morbidity, mortality, and production losses in livestock, with economic consequences for cattle and sheep industries. Despite their growing impact due to environmental and anthropogenic changes, little is known of the prevalence of these viruses in North American bison (Bison bison). We present the first cross-sectional survey of BTV and EHDV in North American bison, with samples collected from 287 animals across 9 herds in 7 U.S. states from September to November 2023. Using competitive enzyme-linked immunosorbent assays (cELISA), we detected seroprevalence rates of 56.5% for BTV and 57.5% for EHDV. We found higher seroprevalence in North American bison compared to reports in European bison populations, suggesting that bison could potentially serve as incidental hosts of orbiviruses during key transmission periods; however, their role in virus transmission remains uncertain and warrants further investigation, particularly regarding the duration of viremia, potential amplification capacity, and year-to-year variability in PCR positivity. Logistic regression analysis revealed age as a significant predictor for both BTV (OR: 1.15, CI: 1.05–1.26, p: 0.006) and EHDV (OR: 1.16, CI: 1.06–1.28, p: 0.0014) seropositivity. PCR amplification identified circulating BTV serotypes 6, 11, 13, 17. Additionally, age was negatively associated with PCR positivity for both BTV (OR: 0.70, CI: 0.53–0.93, p: 0.014) and EHDV (OR: 0.56, CI: 0.33–0.93, p: 0.024), suggesting a decline in detectable viremia with increasing age. Although complex environmental and epidemiological factors likely play a role, this trend may be due to older animals having experienced more vector seasons, thereby increasing their cumulative exposure and subsequent immunity to these viruses over time. The significant age-associated dynamics reveal the importance of considering life stage in disease surveillance and management. Our study also highlights the importance of integrating bison into future vector-borne disease research and control strategies to mitigate risks to livestock, wildlife, and ecosystem health.
O. P. Yavorovskyi, A. V. Ragulya, V. M. Riabovol
et al.
The aim: to study the influence of structural, spectral and quantum-chemical parameters of the synthesized TiO2, TiO2/Ag (4 wt. %) and TiO2/Ag (8 wt. %) nanosystems on biological activity.
Materials and methods. The structural-morphological, spectral, toxicological and cytotoxic properties of TiO2 nanomaterials with silver content in the range from 0 wt % to 8 wt. % for the direction of human biosafety were investigated. The TiO2/Ag composites were characterized by X-ray diffraction, transmission electron microscopy, Raman spectroscopy, and the results of high-level quantum chemical calculations.
Results. The optical activity of the TiO2/Ag composite was determined by Raman spectroscopy, which is confirmed by the shift in the Eg1 mode frequency from 143 cm-1 to 157 cm-1 and the FWHM in the range from 12 cm-1 to 19 cm-1 due to the decrease in the size of the TiO2 crystallites. The mode shift in nano-TiO2/Ag reflects a certain deformation of the anatase-modified titanium dioxide crystal lattice upon doping with silver. This leads to an increase in the ability to produce reactive oxygen species on the surface of the TiO2/Ag nanoparticle and to an increase in biological activity (4 wt. % Ag; 8 wt. % Ag) compared to undoped TiO2, providing an increase in their toxicity, which is confirmed by the values LD50, CC50 parameters, respectively. According to the results of quantum chemical calculations, it was established that during the adsorption of the Ag2 dimer on the surface of anatase in the Ti15O41H22Ag2 adsorption complex, two Ag atoms are involved with the formation of four Ag–O bonds, the length of which with the two-coordinated oxygen atoms of the TiO2 surface is 2.44 Å, and the Ag–Ag bond length increases to 2.75 Å, compared to the equilibrium distance in the diatomic Ag2 molecule (2.53 Å). This indicates the vibrationally excited state of the Ag2 diatomic fragment in the Ti15O41H22Ag2 adsorption complex. It should also be noted that the ionization potential of the adsorption complex decreased from 7.35 eV to 5.72 eV. The result of such changes is the increased reactivity of argentum atoms compared to their reactivity in the diatomic Ag2 molecule. Due to the fact that silver atoms adsorbed on the surface of anatase nanoparticles act as electron traps, the efficiency of separation of photogenerated electron-hole pairs (excitons) with interphase electron transfer increases, which increases the photocatalytic and biocidal properties of silver-doped anatase.
Conclusions. There is a certain objective relationship between the physicochemical parameters of nanoparticles and their biological activity, which can be characterized not only qualitatively, but also quantitatively. Thus, in the materials of our research, the influence of their size, specific surface area, the presence of hydroxyl groups on the surface of the nanoparticle, the size of crystallites, the size of interatomic bonds, and the ionization potential on the toxicity of nanoparticles has been demonstrated. These data are of great scientific importance not only in terms of their hygienic regulation, but also in terms of further synthesis of safer nanomaterials.
Farhan Kursheed, Asraar Tabassum, Umme Farwa
et al.
Background and Objectives: Antimicrobial resistance has emerged as a significant global health threat. Infections caused by Multi Drug-Resistant (MDR) bacteria pose formidable challenges in terms of treatment options and patient outcomes. Pus cultures serve as crucial diagnostic tools in identifying the agents responsible for various infections, and their antimicrobial susceptibility patterns which help in establishment of empirical therapy guidelines. This study was conducted to determine the pathogen and its susceptibility pattern from pus cultures and to generate antibiogram in our tertiary care setting.
Materials and Methods: It was a cross-sectional study, conducted for a period of six months, from July 2022 to December 2022, in the Pathology Department of Pakistan Institute of Medical Sciences (PIMS).
Results: Out of total 2507 samples received, 1242 (49.5%) showed positive culture. Among the 1242 positive samples, 364 were Gram positive cocci (GPCs) and 878 were Gram negative rods (GNRs). Methicillin resistant Staphylococcus aureus (MRSA) was the most common isolate (23%) followed by Klebsiella pneumoniae (22.6%), Pseudomonas aeruginosa (16.9%), Enterobacter spp. (15.5%) and Escherichia coli (14.2%). Vancomycin was found to be highly effective (100%) against MRSA. GPCs were highly susceptible to linezolid (98%) while GNRs showed high level of sensitivity to colistin (96%) and tigecycline (92%).
Conclusion: The generation of a local antibiogram specific to the hospital setting is essential to effectively manage infections empirically and preserve the efficacy of existing antibiotics. By implementing antimicrobial stewardship practices based on a better understanding of antibiotic susceptibility patterns, we can contribute to the mitigation of antibiotic resistance and improve patient outcomes.
L’articolo analizza la rilevanza che riveste la proliferazione incontrollata di armi di provenienza legale e illegale nell’attuale scenario messicano di crisi umanitaria, con particolare riferimento al ruolo che giocano gli Stati Uniti, l’Italia e in generale gli interessi collegati alla produzione e al commercio di armi. Si prendono, inoltre, in considerazione le azioni più recenti del governo federale messicano nell'ambito di una strategia giuridica volta a contrastare il traffico di armi e la violenza armata nel Paese e a promuovere la tutela dei diritti umani.
Social pathology. Social and public welfare. Criminology
Sarang S. Talwelkar, Iris A.K. Lähdeniemi, Mikko I. Mäyränpää
et al.
Summary: Drug sensitivity data acquired from solid tumor-derived cultures are often unsuitable for personalized treatment guidance due to the lengthy turnaround time. Here, we present a protocol for determining ex vivo drug sensitivities using fresh uncultured human lung tumor-derived EpCAM+ epithelial cells (FUTCs). We describe steps for drug testing in FUTCs to identify tumor cell-selective single or combination therapy in 72 h of sample processing. The FUTC-based approach can also be used to predict in vivo resistance to known targeted therapies.For complete details on the use and execution of this protocol, please refer to Talwelkar et al. (2021). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
Lucia Taramasso, Antonio Falletta, Elena Ricci
et al.
The aim of the present study was to evaluate CD4/CD8 dynamics in patients on dolutegravir (DTG)-based two-drug regimens (2DRs) and compare them with DTG-containing triple-drug regimens (3DRs). A prospective observational study was performed in the context of the SCOLTA cohort. Experienced PWH with HIV-RNA < 50 copies/mL were included if they were on the DTG-2DR, the DTG + tenofovir/emtricitabine (TDF/FTC) regimen, the DTG + tenofovir alafenamide (TAF)/FTC regimen, or the DTG + abacavir/lamivudine (ABC/3TC) regimen; they were followed-up for at least one year. A total of 533 PWH were enrolled, 120 in the DTG + 3TC group, 38 in the DTG + protease inhibitors (PI) group, 67 in the DTG + rilpivirine (RPV) group, 49 in the DTG + TDF/FTC group, 27 in the DTG + TAF/FTC group, and 232 in the DTG + ABC/3TC group. After one year, the CD4/CD8 ratio significantly increased in the PWH treated with DTG + 3TC (+0.08 ± 0.26), DTG + TDF/FTC (+0.1 ± 0.19), and DTG + ABC/3TC (+0.08 ± 0.25). At two years, the CD4/CD8 increase was confirmed for PWH on DTG + TDF/FTC (+0.16 ± 0.28) and DTG + ABC/3TC (+0.1 ± 0.3). In the SCOLTA cohort, PWH on 2DRs experienced a CD4/CD8 increase only in the DTG + 3TC group. Controlled studies with longer follow-up will clarify the long-term immunological and clinical impacts of DTG-2DR.
Nicholas Embleton, Janet Berrington, Stephen Cummings
et al.
Background: Preterm infants have high rates of morbidity, especially from late-onset sepsis and necrotising enterocolitis. Lactoferrin is an anti-infective milk protein that may act through effects on gut bacteria, metabolites and epithelial cell function. The impact of supplemental lactoferrin in reducing late-onset sepsis was explored in the Enteral LactoFerrin In Neonates (ELFIN) trial. Objectives: The Mechanisms Affecting the Gut of Preterm Infants in Enteral feeding (MAGPIE) study was nested within the ELFIN trial and aimed to determine the impact of lactoferrin on gut microbiota and bacterial function, and changes preceding disease onset. We aimed to explore impacts on the stool bacteria and faecal/urinary metabolome using gas and liquid chromatography–mass spectrometry, and explore immunohistological pathways in resected tissue. Methods: Preterm infants from 12 NHS hospitals were enrolled in the study, and daily stool and urine samples were collected. Local sample collection data were combined with ELFIN trial data from the National Perinatal Epidemiology Unit, Oxford. The longitudinal impact of lactoferrin in healthy infants was determined, and samples that were collected before disease onset were matched with samples from healthy control infants. Established, quality-controlled 16S ribonucleic acid, gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry analyses were conducted. Validated databases and standardised workflows were used to identify bacteria and metabolites. Tissue samples from infants undergoing surgery and matched controls were analysed. Results: We recruited 479 preterm infants (mean gestation of 28.4 ± 2.3 weeks) and collected > 33,000 usable samples from 467 infants. 16S ribonucleic acid bacterial analysis was conducted on samples from 201 infants, of whom 20 had necrotising enterocolitis and 51 had late-onset sepsis, along with samples from healthy matched controls to explore longitudinal changes. The greatest change in relative bacterial abundance over time was observed in Staphylococcus, which decreased from 42% at aged 7–9 days to only 2% at aged 30–60 days (p < 0.001). Small but significant differences in community composition were observed between samples in each ELFIN trial group (R2 = 0.005; p = 0.04). Staphylococcus (p < 0.01), Haemophilus (p < 0.01) and Lactobacillus (p = 0.01) showed greater mean relative abundance in the placebo group than in the lactoferrin group. Gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry analyses showed that lactoferrin had limited impact on the metabolome. Liquid chromatography–mass spectrometry showed significant metabolite differences between necrotising enterocolitis or late-onset sepsis infants and healthy controls. The resected gut tissue analysis revealed 82 differentially expressed genes between healthy and necrotic tissue. Limitations: Although we recruited a large number of infants, collecting daily samples from every infant is challenging, especially in the few days immediately preceding disease onset. Conclusion: We conducted a large mechanistic study across multiple hospital sites and showed that, although lactoferrin significantly decreased the level of Staphylococcus and other key pathogens, the impact was smaller than those of other clinical variables. Immunohistochemistry identified multiple inflammatory pathways leading to necrotising enterocolitis and showed that the use of NHS pathology archive tissue is feasible in the context of a randomised controlled trial. Future work: We observed significant changes in the stool and urinary metabolome in cases preceding late-onset sepsis or necrotising enterocolitis, which provide metabolic targets for a future mechanistic and biomarker study. Trial registration: Current Controlled Trials ISRCTN12554594. Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 14. See the NIHR Journals Library website for further project information.
Francesco Valeri, Malena dos Santos Guilherme, Fuqian He
et al.
Alzheimer’s disease is a progressive neurodegenerative disorder affecting around 30 million patients worldwide. The predominant sporadic variant remains enigmatic as the underlying cause has still not been identified. Since efficient therapeutic treatments are still lacking, the microbiome and its manipulation have been considered as a new, innovative approach. 5xFAD Alzheimer’s disease model mice were subjected to one-time fecal material transfer after antibiotics-treatment using two types of inoculation: material derived from the caecum of age-matched (young) wild type mice or from middle aged, 1 year old (old) wild type mice. Mice were profiled after transfer for physiological parameters, microbiome, behavioral tasks, and amyloid deposition. A single time transfer of cecal material from the older donor group established an aged phenotype in the recipient animals as indicated by elevated cultivatable fecal Enterobacteriaceae and Lactobacillaceae representative bacteria, a decreased Firmicutes amount as assessed by qPCR, and by increased levels of serum LPS binding protein. While behavioral deficits were not accelerated, single brain regions (prefrontal cortex and dentate gyrus) showed higher plaque load after transfer of material from older animals. We could demonstrate that the age of the donor of cecal material might affect early pathological hallmarks of Alzheimer’s disease. This could be relevant when considering new microbiome-based therapies for this devastating disorder.