Neuroinflammation in a Mouse Model of Alzheimer's Disease versus Auditory Dysfunction: Machine Learning...

Area of Science:

• Neuroscience
• Auditory System Research
• Alzheimer's Disease Pathogenesis

Background:

• Auditory dysfunction, including central auditory hyperactivity, is observed in 5xFAD Alzheimer's disease (AD) mouse models.
• Amyloidosis in AD may causally link to auditory dysfunction, with hyperactivity correlating to plaque deposition in auditory midbrain and thalamus.
• Neuroinflammation is proposed as a link between central auditory hyperactivity and AD, but its role in the auditory pathway remains uninvestigated in amyloidosis models.

Approach:

• Machine learning was employed to classify auditory brainstem responses (ABRs) in 5xFAD mice and wild-type (WT) littermates.
• Neuroinflammation was assessed in auditory cortical, thalamic, and brainstem regions.
• Cochlear pathology and behavioral changes (fear conditioning, open field, novel object recognition) were also evaluated.

Key Points:

• Machine learning reliably classified ABRs in 6-month and 12-month-old 5xFAD mice, with Waves IV and V characteristics being key features.
• Significant microglial and astrocytic activation were observed in the inferior colliculus and medial geniculate body of 5xFAD mice at 6 months.
• Auditory inflammation was present in cortical centers but not in lower brainstem regions; no cochlear neuronal or synaptic loss was detected.
• 5xFAD mice exhibited reduced tone responses in fear conditioning tests starting at 6 months.

Conclusions:

• Serial auditory brainstem response (ABR) measurements show promise for early, cost-effective detection of neuroinflammation in auditory processing centers in AD patients.
• Central auditory hyperactivity may serve as a potential biomarker for AD progression.
• Auditory processing changes can help stratify AD patients into distinct clinical populations.