TY - JOUR
T1 - Increased Gain in the Auditory Pathway, Alzheimer's Disease Continuum, and Air Pollution
T2 - Peripheral and Central Auditory System Dysfunction Evolves Across Pediatric and Adult Urbanites
AU - Calderón-Garcidueñas, Lilian
AU - Kulesza, Randy J.
AU - Mansour, Yusra
AU - Aiello-Mora, Mario
AU - Mukherjee, Partha S.
AU - González-González, Luis Oscar
N1 - Publisher Copyright:
© 2019 - IOS Press and the authors.
PY - 2019
Y1 - 2019
N2 - 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 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.
AB - 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 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.
KW - Air pollution
KW - Alzheimer's disease continuum
KW - alpha synuclein
KW - auditory gain
KW - auditory nuclei
KW - auditory plasticity
KW - brainstem auditory evoked potentials
KW - children
KW - combustion and friction-derived nanoparticles
KW - hyperphosphorylated tau
UR - http://www.scopus.com/inward/record.url?scp=85071258249&partnerID=8YFLogxK
U2 - 10.3233/JAD-190405
DO - 10.3233/JAD-190405
M3 - Article
C2 - 31322574
AN - SCOPUS:85071258249
SN - 1387-2877
VL - 70
SP - 1275
EP - 1286
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -