Brain beta-amyloid pathology is linked to stria vascularis pathology and hearing loss – evidence from two Alzheimer´s disease mouse models

Presbycusis is a main risk for Alzheimer´s disease (AD).Links are unknown.We tested whether amyloid b (Ab) deposition in the brain results in hearing pathology.

We use two genetically modified mice.The 3xTg-AD overexpresses mutated amyloid precursor protein (APP), with Ab deposits in the brain. The "knock-in" APPNL-F expresses mutated "humanized" APP with no overexpression, and Ab deposits in brain regions affected in AD. Mice were assigned to "young" (2-4 months) "adult" (6-9 months) and "old" (past 10 months) age groups. Auditory brainstem recordings (ABRs), "in vivo" cochlear imaging with [18F]FDG PET, histology and immunocytochemistry for inflammatory markers were used.

PET scans showed a trend (p=0.079) in SUVgluc towards lower glucose metabolism in the cochlea of old AD mice (3.83±0.69) as compared to young (6.50±2.55). There was atrophy of the stria vascularis (SV,) more evident in old mice. Immunocytochemistry for Iba1, marker for activated macrophages, labeled the SV of adult TgAD mice. They were more abundant in old mice, invading the spiral ligament. Histological findings were similar in APP mice. ABRs showed significantly increased auditory thresholds relative to wild type mice, starting in the high frequencies and extending to lower frequencies at the old age group.

Massive dysregulation of APP in the 3xTg-AD mouse or dysregulation restricted to the cortex in the APP mouse led to SV pathology. Ab deposition may result in faulty clearance in blood vessels, including the SV, with dysregulated inflammation, SV damage and altered endocochlear potential with hearing loss, suggesting a vicious circle between AD and presbycusis.

Supported by Cluster of Excellence "Hearing4all", EXC 2177/1, 390895286, German Research Foundation, DFG and by Internationale Hörstiftung.

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