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Here, we identified long, thin dendritic filopodia that establish direct dendrite-to-dendrite contacts, forming dendritic nanotubes (DNTs) in mammalian brains. Using super-resolution microscopy, we characterized their unique molecular composition and dynamics in dissociated neurons, enabling Ca\n                  <jats:sup>2+<\/jats:sup>\n                  propagation over distances. Utilizing imaging and machine-learning-based analysis, we confirmed the\n                  <jats:italic>in situ<\/jats:italic>\n                  presence of DNTs connecting dendrites to other dendrites whose anatomical features are distinguished from synaptic dendritic spines. DNTs mediate the active transport of small molecules or human amyloid-beta (A\u03b2), implicating the role of DNT network in AD pathology. Notably, DNT levels increased prior to the onset of amyloid plaque deposits in the mPFC of APP\/PS1 mice. Computational simulations predicted the progression of amyloidosis, providing insight into the mechanisms underlying neurodegeneration through these DNTs. This study unveils a previously unrecognized nanotubular network, highlighting another dimension of neuronal connectivity beyond synapses.\n                <\/jats:p>","DOI":"10.1101\/2025.05.20.655147","type":"posted-content","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T19:55:14Z","timestamp":1747857314000},"source":"Crossref","is-referenced-by-count":1,"title":["Intercellular communication in the brain via dendritic nanotubular network"],"prefix":"10.64898","author":[{"given":"Minhyeok","family":"Chang","sequence":"first","affiliation":[{"name":"The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Kr\u00fcssel","sequence":"additional","affiliation":[{"name":"The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laxmi Kumar","family":"Parajuli","sequence":"additional","affiliation":[{"name":"Department of Cellular Neurobiology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lee","sequence":"additional","affiliation":[{"name":"The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alec","family":"Merodio","sequence":"additional","affiliation":[{"name":"The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeyoung","family":"Kwon","sequence":"additional","affiliation":[{"name":"The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Okabe","sequence":"additional","affiliation":[{"name":"Department of Cellular Neurobiology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung-Bae","family":"Kwon","sequence":"additional","affiliation":[{"name":"The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA"},{"name":"Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041122444080000_2025.05.20.655147v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80771-0"},{"key":"2026041122444080000_2025.05.20.655147v1.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198949"},{"key":"2026041122444080000_2025.05.20.655147v1.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1093133"},{"key":"2026041122444080000_2025.05.20.655147v1.4","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.083279"},{"key":"2026041122444080000_2025.05.20.655147v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2589-x"},{"key":"2026041122444080000_2025.05.20.655147v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2021.09.007"},{"key":"2026041122444080000_2025.05.20.655147v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2406"},{"key":"2026041122444080000_2025.05.20.655147v1.8","doi-asserted-by":"publisher","DOI":"10.1242\/dev.086223"},{"key":"2026041122444080000_2025.05.20.655147v1.9","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj3995"},{"key":"2026041122444080000_2025.05.20.655147v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2010.147"},{"key":"2026041122444080000_2025.05.20.655147v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.177"},{"key":"2026041122444080000_2025.05.20.655147v1.12","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-015-0269-0"},{"key":"2026041122444080000_2025.05.20.655147v1.13","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018101230"},{"key":"2026041122444080000_2025.05.20.655147v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2022.11.043"},{"key":"2026041122444080000_2025.05.20.655147v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.05.025"},{"key":"2026041122444080000_2025.05.20.655147v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/nature09986"},{"key":"2026041122444080000_2025.05.20.655147v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05483-6"},{"key":"2026041122444080000_2025.05.20.655147v1.18","doi-asserted-by":"crossref","unstructured":"J. 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