Summary: While conducting experiments in mice, researchers stumbled upon a correlation between Alzheimer’s disease plaques and hearing loss. In one transgenic mouse model of Alzheimer’s, older mice exhibited hearing changes akin to those observed in humans with Alzheimer’s.
The critical factor appeared to be the location of amyloid beta protein plaques, with hearing impairment linked to plaques on the auditory brainstem.
This finding could offer a new approach to tracking Alzheimer’s disease progression and inform diagnostic practices.
The research involved two different transgenic mouse models of Alzheimer’s disease, both of which were designed to produce amyloid beta protein, the main component of the plaques associated with Alzheimer’s.
The study revealed that plaques in certain parts of the brain, such as the hippocampus and auditory cortex, didn’t appear to have a substantial impact on hearing loss. The crucial factor seemed to be the presence of plaques in the auditory brainstem.
Researchers found that the plaques on the auditory brainstem impeded the area’s ability to coordinate responses to sound, potentially explaining why some Alzheimer’s patients experience auditory symptoms.
Source: University of Rochester
Science lends itself to questions, changing hypotheses, and chance findings. Recently, in the White Lab at the Del Monte Institute for Neuroscience at the University of Rochester, Neuroscience graduate student Daxiang Na was reviewing data for one project but instead uncovered something unexpected. He discovered that where plaques associated with Alzheimer’s disease are found in the brain may contribute to hearing loss.
Na was conducting hearing tests on mice with amyloid beta, the main component of protein plaques and tangles found in Alzheimer’s. While looking at two different transgenic mouse models of the disease, he found for one model, called 5xFAD, the older mice had hearing changes similar to what is found in people with Alzheimer’s disease. The other model did not demonstrate these hearing changes, nor did younger mice in the 5xFAD group.
“It was a chance observation,” said Na, who is first author of a paper with these findings in Frontiers in Neuroscience.
“Both mouse models had amyloid beta protein, but where we found the plaque varied, and that may be why hearing loss varied across the groups.”
Researchers found that the brains of older mice from both models had plaques in the hippocampus and auditory cortex. But the brain of mice with hearing changes also had a small amount of plaque on the auditory brainstem, suggesting this area may be sensitive to disruption from plaque found in Alzheimer’s. Researchers discovered that the plaque reduced the brainstem’s ability to coordinate responses to sound.
“This may explain why Alzheimer’s patients have auditory symptoms,” said Patricia White, PhD, professor of Neuroscience and senior author of the study.
“We think the location of plaques may be more important to hearing decline. It could be a potential biomarker to track disease progression because it could be assessed with amyloid PET imaging.
“Our data also suggest that regular auditory Brainstem Response assessments could help with diagnosis.”
Additional authors include Jingyuan Zhang, PhD, Holly Beaulac, PhD, Dorota Piekna-Przybylska, PhD, Paige Nicklas, and Amy Kiernan, PhD, of the University of Rochester Medical Center.
Funding: This research was supported by the National Institute of Health, the National Institute on Aging.
About this Alzheimer’s disease and hearing loss research news
Increased central auditory gain in 5xFAD Alzheimer’s disease mice as an early biomarker candidate for Alzheimer’s disease diagnosis
Alzheimer’s Disease (AD) is a neurodegenerative illness without a cure. All current therapies require an accurate diagnosis and staging of AD to ensure appropriate care. Central auditory processing disorders (CAPDs) and hearing loss have been associated with AD, and may precede the onset of Alzheimer’s dementia. Therefore, CAPD is a possible biomarker candidate for AD diagnosis.
However, little is known about how CAPD and AD pathological changes are correlated. In the present study, we investigated auditory changes in AD using transgenic amyloidosis mouse models. AD mouse models were bred to a mouse strain commonly used for auditory experiments, to compensate for the recessive accelerated hearing loss on the parent background.
Auditory brainstem response (ABR) recordings revealed significant hearing loss, a reduced ABR wave I amplitude, and increased central gain in 5xFAD mice. In comparison, these effects were milder or reversed in APP/PS1 mice.
Longitudinal analyses revealed that in 5xFAD mice, central gain increase preceded ABR wave I amplitude reduction and hearing loss, suggesting that it may originate from lesions in the central nervous system rather than the peripheral loss. Pharmacologically facilitating cholinergic signaling with donepezil reversed the central gain in 5xFAD mice.
After the central gain increased, aging 5xFAD mice developed deficits for hearing sound pips in the presence of noise, consistent with CAPD-like symptoms of AD patients. Histological analysis revealed that amyloid plaques were deposited in the auditory cortex of both mouse strains.
However, in 5xFAD but not APP/PS1 mice, plaque was observed in the upper auditory brainstem, specifically the inferior colliculus (IC) and the medial geniculate body (MGB). This plaque distribution parallels histological findings from human subjects with AD and correlates in age with central gain increase.
Overall, we conclude that auditory alterations in amyloidosis mouse models correlate with amyloid deposits in the auditory brainstem and may be reversed initially through enhanced cholinergic signaling.
The alteration of ABR recording related to the increase in central gain prior to AD-related hearing disorders suggests that it could potentially be used as an early biomarker of AD diagnosis.