{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:03:40Z","timestamp":1784027020694,"version":"3.55.0"},"reference-count":43,"publisher":"IOP Publishing","issue":"4","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/iop-standard\/v1"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["52237010"],"award-info":[{"award-number":["52237010"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","award":["2024IAIS-ZD005"],"award-info":[{"award-number":["2024IAIS-ZD005"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["J. Neural Eng."],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Objective.<\/jats:italic>\n                    Hippocampal\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -amyloid (A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    ) pathology may induce early circuit dysfunction and memory impairment in Alzheimer\u2019s disease (AD), making it a key target for slowing disease progression. However, existing transcranial electrical stimulation approaches, while remaining within safety limits, are insufficient to non-invasively generate sufficiently strong electric fields in deep brain regions. Here, we investigated whether nanosecond transcranial pulsed electric field stimulation (ns-tPFS) could provide a non-invasive deep-target strategy for modulating hippocampal A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    pathology in an AD model.\n                    <jats:italic>Approach.<\/jats:italic>\n                    The ten-month-old 5xFAD mice were selected for delivering repeated ns-tPFS (500 ns, 500 V, 1 Hz). The intracranial electric field exposure was estimated using finite-element modeling (FEM). Treatment effects were evaluated using the Morris water maze,\n                    <jats:italic>Y<\/jats:italic>\n                    -maze, immunofluorescence of A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    deposition in the hippocampus and cortex, and western blotting of A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -related proteins. In addition, the structural responses of A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    oligomers to pulsed electric fields were examined by employing molecular dynamics (MD) simulations, and structural brain safety was assessed by 9.4 T small-animal magnetic resonance imaging (MRI).\n                    <jats:italic>Main results.<\/jats:italic>\n                    ns-tPFS generated transient hippocampal electric fields on the order of 10\n                    <jats:sup>4<\/jats:sup>\n                    V m\n                    <jats:sup>\u22121<\/jats:sup>\n                    . It reduced the hippocampal A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    burden and was associated with coordinated changes in A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -related pathways, including decreased amyloidogenic processing and modulated A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    transport-related receptors. MD simulations further suggested that A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    oligomers are structurally sensitive to nanosecond-scale electric field transients within the hippocampal field range estimated by FEM. These changes were accompanied by improved spatial and working memory in 5xFAD mice. In contrast, under the present stimulation regimen, healthy mice were observed with no detectable cognitive impairment, or macroscopic MRI abnormalities.\n                    <jats:italic>Significance.<\/jats:italic>\n                    ns-tPFS may be a promising non-invasive deep-target electric-field strategy for mitigating hippocampal A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    pathology and improving cognitive performance in an AD mouse model.\n                  <\/jats:p>","DOI":"10.1088\/1741-2552\/ae8579","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T22:52:02Z","timestamp":1783032722000},"page":"046016","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-invasive nanosecond transcranial pulsed electric fields: a deep-penetrating, high-field stimulation that suppresses hippocampal\n                    <i>\u03b2<\/i>\n                    -amyloid and improves cognitive deficits in Alzheimer\u2019s disease model"],"prefix":"10.1088","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6898-4942","authenticated-orcid":true,"given":"Yue","family":"Chen","sequence":"first","affiliation":[{"name":"Chongqing University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanping","family":"Yan","sequence":"additional","affiliation":[{"name":"Chongqing University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pangxin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Chongqing University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyi","family":"Li","sequence":"additional","affiliation":[{"name":"Chongqing University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Yu","sequence":"additional","affiliation":[{"name":"Chongqing University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6104-0282","authenticated-orcid":true,"given":"Shoulong","family":"Dong","sequence":"additional","affiliation":[{"name":"Chongqing University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1781-2756","authenticated-orcid":true,"given":"Chenguo","family":"Yao","sequence":"additional","affiliation":[{"name":"Chongqing University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"jneae8579bib1","article-title":"World Alzheimer report 2025: reimagining life with dementia-the power of rehabilitation","author":"Alzheimer\u2019s Disease International","year":"2025","type":"report"},{"key":"jneae8579bib2","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1021\/acs.chemrev.0c01122","type":"journal-article","article-title":"Amyloid oligomers: a joint experimental\/computational perspective on Alzheimer\u2019s disease, Parkinson\u2019s disease, type II diabetes, and amyotrophic lateral sclerosis","volume":"121","author":"Nguyen","year":"2021","journal-title":"Chem. 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All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2026-03-25","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-07-01","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-07-14","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}