Increased Gain in the Auditory Pathway, Alzheimer’s Disease Continuum, and Air Pollution: Peripheral and Central Auditory System Dysfunction Evolves Across Pediatric and Adult Urbanites

Article type: Research Article

Authors: Calderón-Garcidueñas, Lilian^{a; b; *} | Kulesza, Randy J.^c | Mansour, Yusra^c | Aiello-Mora, Mario^d | Mukherjee, Partha S.^e | González-González, Luis Oscar^f

Affiliations: [a] The University of Montana, Missoula, MT, USA | [b] Universidad del Valle de México, México | [c] Auditory Research Center, Lake Erie College of Osteopathic Medicine, Erie, PA, USA | [d] Servicio de Otorrinolaringologia, Instituto Nacional de Cardiología, Mexico | [e] Indian Statistical Institute, Kolkata, India | [f] Instituto Nacional de Pediatría, México

Correspondence: [*] Correspondence to: Professor Lilian Calderón-Garcidueñas, MA, MD, PhD, University of Montana, 32 Campus Drive, 287 Skaggs Building, Missoula, MT 59812, USA. Tel.: +1 406 243 4785; E-mail: [email protected].

Abstract: A major impediment in early diagnosis of Alzheimer’s disease (AD) is the lack of robust non-invasive biomarkers of early brain dysfunction. Metropolitan Mexico City (MMC) children and young adults show hyperphosphorylated tau, amyloid-β, and α-synuclein within auditory and vestibular nuclei and marked dysmorphology in the ventral cochlear nucleus and superior olivary complex. Based on early involvement of auditory brainstem centers, we believe brainstem auditory evoked potentials can provide early AD biomarkers in MMC young residents. We measured brainstem auditory evoked potentials in MMC clinically healthy children (8.52±3.3 years) and adults (21.08±3.0 years, 42.48±8.5 years, and 71.2±6.4 years) compared to clean air controls (6.5±0.7 years) and used multivariate analysis adjusting for age, gender, and residency. MMC children had decreased latency to wave I, delays in waves III and V, and longer latencies for interwave intervals, consistent with delayed central conduction time of brainstem neural transmission. In sharp contrast, young adults have significantly shortened interwave intervals I–III and I–V. By the 5th decade, wave V and interval I–V were significantly shorter, while the elderly cohort had significant delay in mean latencies and interwave intervals. Compensatory plasticity, increased auditory gain, cochlear synaptopathy, neuroinflammation, and AD continuum likely play a role in the evolving distinct auditory pathology in megacity urbanites. Understanding auditory central and peripheral dysfunction in the AD continuum evolving and progressing in pediatric and young adult populations may shed light on the complex mechanisms of AD development and help identify strong noninvasive biomarkers. AD evolving from childhood in air pollution environments ought to be preventable.

Keywords: Air pollution, alpha synuclein, Alzheimer’s disease continuum, auditory nuclei, auditory plasticity, auditory gain, brainstem auditory evoked potentials, children, hyperphosphorylated tau, combustion and friction-derived nanoparticles

DOI: 10.3233/JAD-190405

Journal: Journal of Alzheimer's Disease, vol. 70, no. 4, pp. 1275-1286, 2019