Auditory Brainstem Dysfunction, Non-Invasive Biomarkers for Early Diagnosis and Monitoring of Alzheimer’s Disease in Young Urban Residents Exposed to Air Pollution

Article type: Review Article

Authors: Mansour, Yusra^a | Blackburn, Kaitlyn^b | González-González, Luis Oscar^c | Calderón-Garcidueñas, Lilian^{d; e; 1} | Kulesza, Randy J.^{a; 1; *}

Affiliations: [a] Department of Anatomy, Lake Erie College of Osteopathic Medicine, Erie, PA, USA | [b] Department of Neurology, University of Pittsburgh Medical Center, Erie, PA, USA | [c] Instituto Nacional de Pediatría, México | [d] University of Montana, Missoula, MT, USA | [e] Universidad del Valle de México, México

Correspondence: [*] Randy J. Kulesza, PhD, Department of Anatomy, Lake Erie College of Osteopathic Medicine, 1858 West Grandview Blvd., Erie, PA 16504, USA. Tel.: +1 814 866 8423; E-mail: rkulesza@lecom.edu.

Note: [1] These authors contributed equally to this work.

Abstract: Alzheimer’s disease (AD) is a biological construct defined by abnormal deposits of hyperphosphorylated tau and amyloid-β. The 2050 projection for AD in the USA is 14 million. There is a strong association between AD, air pollution, and traffic. Early diagnosis is imperative for intervention in the initial disease stages. Hearing and, specifically, the ability to encode complex sounds are impaired in AD. Nuclei in the auditory brainstem appear to be sensitive to neurodevelopmental and neurodegenerative disorders. Specifically, sustained exposure to air pollution is harmful to the brainstem; young residents of Metropolitan Mexico City (MMC) exposed to fine particulate matter and combustion-derived nanoparticles develop AD pathology in infancy. MMC clinically healthy children and teens have significant central delays in brainstem auditory evoked potentials (BAEPs). Herein, we review evidence that the auditory pathway is a key site of AD early pathology associated with air pollution and is significantly involved in AD patients. We strongly suggest electrophysiological screening, including BAEPs, be employed to screen individuals for early delays and to monitor progressive decline in patients diagnosed with mild cognitive impairment and AD. Understanding auditory dysfunction in early AD in pediatric and young adult populations may clarify mechanisms of disease progression. Air pollution is a risk factor for the development of AD and as the number of Americans with AD continues to grow without a cure, we need to focus on preventable, early causes of this fatal disease and intervene appropriately.

Keywords: Air Pollution, alzheimer’s continuum, alzheimer’s disease, amyloid-β , brainstem evoked potential, cochlear, combustion-associated nanoparticles, fine particulate matter, hearing, hyperphosphorylated tau, neurofibrillary tangles, PM_2.5 , vestibular nuclei

DOI: 10.3233/JAD-181186

Journal: Journal of Alzheimer's Disease, vol. 67, no. 4, pp. 1147-1155, 2019