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<p>Hearing is the largest modifiable mid-life risk factor for Alzheimer’s 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 <i>Amyloid precursor protein</i>, <i>App</i><sup>S</sup>; 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: <i>App</i><sup>S</sup> separate clearly from healthy humanized (<i>App</i><sup>H</sup>) in sex- and age-dependent manners. Notably, auditory learning during young adulthood shifted the <i>App</i><sup><i>S</i></sup> ABR signature towards a healthy <i>App</i><sup><i>H</i></sup><i>-</i>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月9日

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  • Aysegul Gungor Aydin,
  • Pranav Manoj,
  • Faiza Ramadan,
  • Sarah Rajan,
  • Elias Youssef,
  • Elizabeth B. Torres,
  • Kasia M. Bieszczad

摘要

Hearing is the largest modifiable mid-life risk factor for Alzheimer’s 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.