{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:19:18Z","timestamp":1785410358239,"version":"3.56.0"},"posted":{"date-parts":[[2025,8,11]]},"group-title":"Neuroscience","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01-DC018561 to K.M.B."],"award-info":[{"award-number":["R01-DC018561 to K.M.B."]}],"id":[{"id":"https:\/\/ror.org\/04mhx6838","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Career Continuation Award to E.B.T."],"award-info":[{"award-number":["Career Continuation Award to E.B.T."]}],"id":[{"id":"https:\/\/ror.org\/05r023w67","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,19]]},"abstract":"<jats:p>Hearing is the largest modifiable mid-life risk factor for Alzheimer\u2032s Disease (AD) yet its link to dementia remains unclear. We identified a neurophysiological biomarker of AD risk using the non-invasive, rapidly acquired, and clinically translatable auditory brainstem response (ABR) in normal hearing knock-in rats (Swedish familial AD risk variant to Amyloid precursor protein (AppS); male and female). Human ABRs have been proposed as a biomarker for AD and related dementias. The novel metric reported here is derived from multidimensional parametric feature extraction on the distribution statistics of repeated single-trial ABR traces. We report accurate prediction of genetic risk for AD risk in young and aged rats: AppS separate clearly from healthy humanized (AppH) in sex- and age-dependent manners. Notably, auditory learning during young adulthood shifted the AppS ABR signature towards a healthy AppH-like state that maintained over time into older age. Altogether the findings support the utility of the ABR to track disease state, progression, and effects of intervention, and point to a central neural generator of auditory dysfunction related to AD risk. ABRs could provide a very early biomarker for detection of AD risk and used to test the synergy of auditory and cognitive functions in human dementia.<\/jats:p>","DOI":"10.1101\/2025.08.07.669134","type":"posted-content","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T21:20:30Z","timestamp":1754947230000},"source":"Crossref","is-referenced-by-count":0,"title":["Sound-evoked auditory neurophysiological signals are a window into prodromal functional differences in a preclinical model of Alzheimer\u2032s Disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3398-7959","authenticated-orcid":false,"given":"Aysegul Gungor","family":"Aydin","sequence":"first","affiliation":[{"name":"Biomedical Research Institute of New Jersey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranav","family":"Manoj","sequence":"additional","affiliation":[{"name":"Rutgers University Robert Wood Johnson Medical School;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiza","family":"Ramadan","sequence":"additional","affiliation":[{"name":"Rutgers University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Youssef","sequence":"additional","affiliation":[{"name":"Rutgers University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Rajan","sequence":"additional","affiliation":[{"name":"Rutgers University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4011-3611","authenticated-orcid":false,"given":"Elizabeth","family":"Torres","sequence":"additional","affiliation":[{"name":"Rutgers University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3633-5422","authenticated-orcid":false,"given":"Kasia M","family":"Bieszczad","sequence":"additional","affiliation":[{"name":"Rutgers University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.08.07.669134","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:14:29Z","timestamp":1782278069000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.08.07.669134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,11]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1101\/2025.08.07.669134","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1038\/s41598-026-51854-8","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,8,11]]},"subtype":"preprint"}}