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bioRxiv · 10.1101/2025.08.07.669134

Sound-evoked auditory neurophysiological signals are a window into prodromal functional differences in a preclinical model of Alzheimer's Disease

Aydin, A. G.·Manoj, P.·Ramadan, F.·Youssef, E.·Rajan, S.·Torres, E.·Bieszczad, K. M.
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Abstract

Hearing is the largest modifiable mid-life risk factor for Alzheimers 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.

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Aydin, A. G., Manoj, P., Ramadan, F., Youssef, E., Rajan, S., Torres, E., Bieszczad, K. M.. 2025-08-11. Sound-evoked auditory neurophysiological signals are a window into prodromal functional differences in a preclinical model of Alzheimer's Disease. https://doi.org/10.1101/2025.08.07.669134

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