Early Functional and Cognitive Declines Measured by Auditory-Evoked Cortical Potentials in Mice With Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is characterized by a progressive loss of memory and cognitive decline. However, the assessment of AD-associated functional and cognitive changes is still a big challenge. Auditory-evoked cortical potential (AECP) is an event-related potential reflecting not only neural activation in the auditory cortex (AC) but also cognitive activity in the brain. In this study, we used the subdermal needle electrodes with the same electrode setting as the auditory brainstem response (ABR) recording and recorded AECP in normal aging CBA/CaJ mice and APP/PS1 AD mice. AECP in mice usually appeared as three positive peaks, i.e., P1, P2, and P3, and three corresponding negative peaks, i.e., N1, N2, and N3. In normal aging CBA mice, the early sensory peaks P1, N1, and P2 were reduced as age increased, whereas the later cognitive peaks N2, P3, and N3 were increased or had no changes with aging. Moreover, the latency of the P1 peak was increased as age increased, although the latencies of later peaks had a significant reduction with aging. In AD mice, peak P1 was significantly reduced in comparison with wild-type (WT) littermates at young ages, proceeding AD phenotype presentation. In particular, the later cognitive peak P3 was diminished after 3 months old, different from the normal aging effect. However, the latencies of AECP peaks in AD mice generally had no significant delay or changes with aging. Finally, consistent with AECP changes, the accumulation of amyloid precursor protein (APP) at the AC was visible in AD mice as early as 2 months old. These data suggest that AECP could serve as an early, non-invasive, and objective biomarker for detecting AD and AD-related dementia (ADRD).

Increased central auditory gain in 5xFAD Alzheimer’s disease mice as an early biomarker candidate for Alzheimer’s disease diagnosis

“…Auditory changes including hearing loss and gap detection deficits have been characterized in several transgenic AD mouse models including 5xFAD and APP/PS1 (O' Leary et al, 2017;Kaylegian et al, 2019;Liu et al, 2020;Weible et al, 2020;Mei et al, 2021). To test if increased central gain occurs in AD mouse models, we performed auditory tests in 5xFAD and APP/PS1 mice at similar ages (5xFAD at 12 months of age and APP/PS1 at 13 months of age), by which time both of the strains have significant plaque accumulation (Jankowsky et al, 2004;Oakley et al, 2006).…”

Update on modifiable risk factors for Alzheimer's disease and related dementias

“…Several lines of preclinical evidence support a link between hearing loss and the AD pathophysiological process. First, several studies using various neurophysiological assessments have reported increased age-related hearing deficits in several AD mouse models, involving both peripheral (including cochlear hair cell loss) and central mechanisms [50,67,78,87]. Second, hearing impairment in AD transgenic mice, modeled either by chronic noise exposure [88] or by chronic perforation of the tympanic membrane (conductive) [59], accelerates cognitive deficits in these mice, likely through enhancing synaptic loss and dysfunction [88].…”

Early Sensory Deficits in Alzheimer’s Disease: A Review of Potential Integrating Diagnostic Methods

“…another report also showed that APP/PS1 mice exhibited normal ASR and PPI at 3 months old, but significantly lower PPI starting from 7 months of age 100 . APP protein expression in the auditory cortex can be detected as early as 2 months old, accompanied by decreased auditory-evoked cortical potential (AECP) 13 . These data indicate that hearing loss and reduced auditory cortical response could be early biomarkers for AD in this mouse model.…”