Early functional and cognitive declines measured by auditory evoked cortical potentials in Alzheimer’s disease mice

Abstract

Alzheimer's disease (AD) is characterized with a progressive loss of memory and cognitive decline. Early detection of AD is critical for prevention and intervention of this common neurodegenerative disease. Previous studies demonstrated that auditory dysfunction could occur at the early stage of AD. Auditory evoked cortical potential (AECP) is an event-related potential reflecting not only neural activation in the auditory cortex but also cognitive activity in the brain. In this study, we recorded AECP in AD mice. AECP in mice usually possessed 3 waveforms. The early sensory P1 and P2 peaks were clearly visible in 1 month old mice. However, the later cognitive P3 peak was not well-developed until the age of 3 months old. In APP/PS1 AD mice, P1 and P2 were reduced at young ages (<6 months old), prior to occurrence of AD phenotypes. Different from normal aging, the cognitive peak of P3 in AD mice was diminished invisible after 4 months old. The latencies of peak N1, P2, and N2 in AD mice before 3 months were shorter than those in WT mice. Consistent with AECP changes, expression of amyloid precursor protein (APP) was visible in the AD mouse auditory cortex at 2 months old. These data indicate that AECP has significant changes in young AD mice and can serve as an early, non-invasive, objective biomarker in AD and AD-related dementia detection and diagnosis.

Stability of neural representations in the auditory midbrain across the lifespan despite age-related brainstem delays

“…Although brainstem, auditory midbrain, and thalamus population processing often is stable in old animals with normal hearing (Lee et al, 2002;Mendelson and Lui, 2004;Osterhagen and Hildebrandt, 2018;Land and Kral, 2022), small effects may cumulate towards higher levels of the auditory system (Mendelson and Lui, 2004;Occelli et al, 2019;Quraishe et al, 2020), affecting the precision of cortical processing, which is critical for temporal and complex sound and processing (Nourski and Brugge, 2011;Nourski et al, 2021aNourski et al, , 2021b. Elongation of cortical potentials is present in aged mice (Mei et al, 2021), and middle latency and cortical evoked potentials in aged humans (Goodin et al, 1978;Dum, 1983;Allison et al, 1984;Martini et al, 1991;Gourévitch and Edeline, 2011;Price et al, 2017;Occelli et al, 2019). This could explain the central aging effects of processing (besides simple latency) on the cortical level (Weible et al, 2014;Occelli et al, 2019), and higher processing stages (Juarez-Salinas et al, 2010).…”