{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:53:04Z","timestamp":1785430384892,"version":"3.56.0"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:00:00Z","timestamp":1775865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008332","name":"Universitat Ramon Llull","doi-asserted-by":"publisher","award":["2025-URL-Proj-007"],"award-info":[{"award-number":["2025-URL-Proj-007"]}],"id":[{"id":"10.13039\/501100008332","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2025-URL-Proj-007"],"award-info":[{"award-number":["2025-URL-Proj-007"]}],"id":[{"id":"https:\/\/ror.org\/04p9k2z50","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"crossref","award":["PID2022-138334OB-I00"],"award-info":[{"award-number":["PID2022-138334OB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is characterized by progressive cognitive decline and the accumulation of amyloid-\u03b2 (A\u03b2) plaques and tau neurofibrillary tangles. Beyond genetic and proteostatic mechanisms, infection- and dysbiosis-based models of AD have gained renewed attention, including the antimicrobial protection hypothesis, in which A\u03b2 may participate in innate immune defense. Here, we reanalyzed ribosomal depleted (Ribo-Zero) RNA-seq data from dorsolateral prefrontal cortex (DLPFC) samples from the Mount Sinai Brain Bank cohort (GSE53697) to screen for non-human transcripts. Reads underwent quality control and adapter trimming, taxonomic classification with Kraken2, abundance re-estimation with Bracken, and differential abundance testing with edgeR. Across 17 samples (9 advanced AD and 8 controls), we detected low-biomass microbial signals, with Acinetobacter radioresistens showing enrichment in the AD group (FDR = 0.018). Several additional taxa showed suggestive group differences but did not remain significant after multiple testing correction, including Lactobacillus iners (FDR = 0.051). We also performed an exploratory in silico analysis of an A. radioresistens biofilm-associated protein homolog, identifying predicted amyloidogenic motifs and surface-exposed regions that may be relevant to cross-seeding hypotheses, although no mechanistic inference can be drawn without experimental validation. Given the technical challenges of inferring microbial signals from post-mortem brain RNA-seq data, including contamination risk, low microbial biomass, and overwhelming host background, these findings should be interpreted as hypothesis-generating and warrant orthogonal validation in larger, microbiome-aware cohorts.<\/jats:p>","DOI":"10.3390\/ijms27083430","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:49:02Z","timestamp":1776070142000},"page":"3430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metatranscriptomic Reanalysis of Alzheimer\u2019s Brains Identifies Low-Biomass Microbial Signals Including Enrichment of Acinetobacter radioresistens"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5781-3799","authenticated-orcid":false,"given":"Francesc X.","family":"Guix","sequence":"first","affiliation":[{"name":"Department of Bioengineering, Institut Qu\u00edmic de Sarri\u00e0 (IQS), Universitat Ramon Llull (URL), 08017 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in early Alzheimer\u2019s disease","volume":"388","author":"Swanson","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1001\/jama.2023.13239","article-title":"Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial","volume":"330","author":"Sims","year":"2023","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s41588-019-0358-2","article-title":"Genetic meta-analysis of diagnosed Alzheimer\u2019s disease identifies new risk loci and implicates A\u03b2, tau, immunity and lipid processing","volume":"51","author":"Kunkle","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Piacentini, R., De Chiara, G., Li Puma, D.D., Ripoli, C., Marcocci, M.E., Garaci, E., Palamara, A.T., and Grassi, C. (2014). HSV-1 and Alzheimer\u2019s disease: More than a hypothesis. Front. Pharmacol., 5.","DOI":"10.3389\/fphar.2014.00097"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.neuron.2018.05.023","article-title":"Multiscale analysis of independent Alzheimer\u2019s cohorts finds disruption of molecular, genetic, and clinical networks by human herpesvirus","volume":"99","author":"Readhead","year":"2018","journal-title":"Neuron"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rizzo, R. (2020). Controversial role of herpesviruses in Alzheimer\u2019s disease. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008575"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.neuron.2019.12.031","article-title":"Human herpesvirus 6 (HHV-6) detection in Alzheimer\u2019s disease cases and controls across multiple cohorts","volume":"105","author":"Allnutt","year":"2020","journal-title":"Neuron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"eaau3333","DOI":"10.1126\/sciadv.aau3333","article-title":"Porphyromonas gingivalis in Alzheimer\u2019s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors","volume":"5","author":"Dominy","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.14283\/jpad.2024.79","article-title":"Periodontal disease and Alzheimer\u2019s: Insights from a systematic literature network analysis","volume":"11","author":"Villar","year":"2024","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.2147\/IDR.S491628","article-title":"Association between Porphyromonas gingivalis and Alzheimer\u2019s disease in older adults: A comprehensive review","volume":"18","year":"2025","journal-title":"Infect. Drug Resist."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Soscia, S.J., Kirby, J.E., Washicosky, K.J., Tucker, S.M., Ingelsson, M., Hyman, B., Burton, M.A., Goldstein, L.E., Duong, S., and Tanzi, R.E. (2010). The Alzheimer\u2019s disease-associated amyloid \u03b2-protein is an antimicrobial peptide. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009505"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/j.jalz.2018.06.3040","article-title":"The antimicrobial protection hypothesis of Alzheimer\u2019s disease","volume":"14","author":"Moir","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.neuron.2018.06.030","article-title":"Alzheimer\u2019s disease-associated \u03b2-amyloid is rapidly seeded by Herpesviridae to protect against brain infection","volume":"99","author":"Eimer","year":"2018","journal-title":"Neuron"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Friedland, R.P., and Chapman, M.R. (2017). The role of microbial amyloid in neurodegeneration. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006654"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature25158","article-title":"Microglia-derived ASC specks cross-seed amyloid-\u03b2 in Alzheimer\u2019s disease","volume":"552","author":"Venegas","year":"2017","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1038\/s41591-024-03201-5","article-title":"The recombinant shingles vaccine is associated with lower risk of dementia","volume":"30","author":"Taquet","year":"2024","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/s41586-025-08800-x","article-title":"A natural experiment on the effect of herpes zoster vaccination on dementia","volume":"641","author":"Eyting","year":"2025","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Salter, S.J., Cox, M.J., Turek, E.M., Calus, S.T., Cookson, W.O., Moffatt, M.F., Turner, P., Parkhill, J., Loman, N.J., and Walker, A.W. (2014). Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol., 12.","DOI":"10.1186\/s12915-014-0087-z"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.tim.2018.11.003","article-title":"Contamination in low microbial biomass microbiome studies: Issues and recommendations","volume":"27","author":"Eisenhofer","year":"2019","journal-title":"Trends Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1038\/s41564-025-02035-2","article-title":"Guidelines for preventing and reporting contamination in low-biomass microbiome studies","volume":"10","author":"Fierer","year":"2025","journal-title":"Nat. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"180185","DOI":"10.1038\/sdata.2018.185","article-title":"The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer\u2019s disease","volume":"5","author":"Wang","year":"2018","journal-title":"Sci. Data"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Amabebe, E., and Anumba, D.O.C. (2018). The vaginal microenvironment: The physiologic role of Lactobacilli. Front. Med., 5.","DOI":"10.3389\/fmed.2018.00181"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zheng, N., Guo, R., Wang, J., Zhou, W., and Ling, Z. (2021). Contribution of Lactobacillus iners to vaginal health and diseases: A systematic review. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.792787"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.resmic.2017.09.003","article-title":"Lactobacillus iners, the unusual suspect","volume":"168","author":"Vaneechoutte","year":"2017","journal-title":"Res. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.cell.2011.02.018","article-title":"Astrocyte\u2013neuron lactate transport is required for long-term memory formation","volume":"144","author":"Suzuki","year":"2011","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12228","DOI":"10.1073\/pnas.1322912111","article-title":"Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons","volume":"111","author":"Yang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/MMBR.00019-15","article-title":"Taxonomy, physiology, and natural products of Actinobacteria","volume":"80","author":"Barka","year":"2015","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ma, Y., Wang, J., Liu, Y., Wang, X., Zhang, B., Zhang, W., Chen, T., Liu, G., Xue, L., and Cui, X. (2023). Nocardioides: \u201cSpecialists\u201d for hard-to-degrade pollutants in the environment. Molecules, 28.","DOI":"10.3390\/molecules28217433"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s13105-012-0184-9","article-title":"6-hydroxy-L-nicotine from Arthrobacter nicotinovorans sustain spatial memory formation by decreasing brain oxidative stress in rats","volume":"69","author":"Hritcu","year":"2013","journal-title":"J. Physiol. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.neulet.2015.02.014","article-title":"Enhanced behavioral response by decreasing brain oxidative stress to 6-hydroxy-L-nicotine in Alzheimer\u2019s disease rat model","volume":"591","author":"Hritcu","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Boiangiu, R.S., Mihasan, M., Gorgan, D.L., Stache, B.A., Petre, B.A., and Hritcu, L. (2020). Cotinine and 6-hydroxy-L-nicotine reverse memory deficits and reduce oxidative stress in A\u03b225\u201335-induced rat model of Alzheimer\u2019s disease. Antioxidants, 9.","DOI":"10.3390\/antiox9080768"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.neuron.2014.12.032","article-title":"Blood\u2013brain barrier breakdown in the aging human hippocampus","volume":"85","author":"Montagne","year":"2015","journal-title":"Neuron"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","article-title":"Blood\u2013brain barrier breakdown is an early biomarker of human cognitive dysfunction","volume":"25","author":"Nation","year":"2019","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"De Gregorio, E., Del Franco, M., Martinucci, M., Roscetto, E., Zarrilli, R., and Di Nocera, P.P. (2015). Biofilm-associated proteins: News from Acinetobacter. BMC Genom., 16.","DOI":"10.1186\/s12864-015-2136-6"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Noble, J.M., Scarmeas, N., Celenti, R.S., Elkind, M.S., Wright, C.B., Schupf, N., and Papapanou, P.N. (2014). Serum IgG antibody levels to periodontal microbiota are associated with incident Alzheimer disease. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114959"},{"key":"ref_37","first-page":"5140259","article-title":"Brain abscess: A rare clinical case with oral etiology","volume":"2022","author":"Pereira","year":"2022","journal-title":"Case Rep. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Emery, D.C., Shoemark, D.K., Batstone, T.E., Waterfall, C.M., Coghill, J.A., Cerajewska, T.L., Davies, M., West, N.X., and Allen, S.J. (2017). 16S rRNA next generation sequencing analysis shows bacteria in Alzheimer\u2019s post-mortem brain. Front. Aging Neurosci., 9.","DOI":"10.3389\/fnagi.2017.00195"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Alonso, R., Pisa, D., Fern\u00e1ndez-Fern\u00e1ndez, A.M., and Carrasco, L. (2018). Infection of fungi and bacteria in brain tissue from elderly persons and patients with Alzheimer\u2019s disease. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00159"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ravaioli, S., De Donno, A., Bottau, G., Campoccia, D., Maso, A., Dolzani, P., Balaji, P., Pegreffi, F., Daglia, M., and Arciola, C.R. (2024). The Opportunistic Pathogen Staphylococcus warneri: Virulence and Antibiotic Resistance, Clinical Features, Association with Orthopedic Implants and Other Medical Devices, and a Glance at Industrial Applications. Antibiotics, 13.","DOI":"10.3390\/antibiotics13100972"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"D19","DOI":"10.1093\/nar\/gkq1019","article-title":"The Sequence Read Archive","volume":"39","author":"Leinonen","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"W537","DOI":"10.1093\/nar\/gky379","article-title":"The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update","volume":"46","author":"Afgan","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_43","unstructured":"Andrews, S. (2010). FastQC: A Quality Control Tool for High Throughput Sequence Data, Babraham Bioinformatics."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1186\/s13059-019-1891-0","article-title":"Improved metagenomic analysis with Kraken 2","volume":"20","author":"Wood","year":"2019","journal-title":"Genome Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e104","DOI":"10.7717\/peerj-cs.104","article-title":"Bracken: Estimating species abundance in metagenomics data","volume":"3","author":"Lu","year":"2017","journal-title":"PeerJ Comput. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ondov, B.D., Bergman, N.H., and Phillippy, A.M. (2011). Interactive metagenomic visualization in a Web browser. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-385"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/s41596-019-0264-1","article-title":"Using MicrobiomeAnalyst for comprehensive statistical, functional, and meta-analysis of microbiome data","volume":"15","author":"Chong","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","article-title":"ColabFold: Making protein folding accessible to all","volume":"19","author":"Mirdita","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nmeth.1432","article-title":"Exploring the sequence determinants of amyloid structure using position-specific scoring matrices","volume":"7","author":"Debulpaep","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/pro.3943","article-title":"UCSF ChimeraX: Structure visualization for researchers, educators, and developers","volume":"30","author":"Pettersen","year":"2021","journal-title":"Protein Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3430\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T04:14:26Z","timestamp":1776140066000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,11]]},"references-count":53,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083430"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083430","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,11]]}}}