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

2021 ◽  
Author(s):  
Yusra Mansour ◽  
Kaitlyn Blackburn ◽  
Luis Oscar González-González ◽  
Lilian Calderón-Garcidueñas ◽  
Randy J. Kulesza
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Early Diagnosis ◽  
Auditory Evoked Potentials ◽  
Strong Association ◽  
Amyloid Β ◽  
Auditory Pathway ◽  
Auditory Brainstem ◽  
Complex Sounds

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.

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

2021 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Randy J. Kulesza ◽  
Yusra Mansour ◽  
Mario Aiello-Mora ◽  
Partha S. Mukherjee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Young Adults ◽  
Evoked Potentials ◽  
Auditory Evoked Potentials ◽  
Auditory Pathway ◽  
Conduction Time ◽  
Brainstem Auditory Evoked Potentials ◽  
Noninvasive Biomarkers

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.

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

2019 ◽  
Vol 67 (4) ◽  
pp. 1147-1155 ◽  
Author(s):  
Yusra Mansour ◽  
Kaitlyn Blackburn ◽  
Luis Oscar González-González ◽  
Lilian Calderón-Garcidueñas ◽  
Randy J. Kulesza
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Early Diagnosis ◽  
Auditory Brainstem ◽  
Urban Residents ◽  
Non Invasive ◽  
Brainstem Dysfunction

Characterizing the Resilience Effect of Neurodegeneration for the Mechanistic Pathway of Alzheimer’s Disease

2021 ◽  
pp. 1-12
Author(s):  
Di Hu ◽  
Chuning Liu ◽  
Kai Xia ◽  
Amy Abramowitz ◽  
Guorong Wu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rapid Development ◽  
Demographic Data ◽  
Strong Association ◽  
Synergetic Effect ◽  
Amyloid Β ◽  
Angular Gyrus ◽  
Limited Attention ◽  
Brain Resilience

Background: With the rapid development of neurobiology and neuroimaging technologies, mounting evidence shows that Alzheimer’s disease (AD) is caused by the build-up of two abnormal proteins, amyloid-β plaques (A) and neurofibrillary tangles (T). Over time, these AD-related neuropathological burdens begin to spread throughout the brain, which results in the characteristic progression of symptoms in AD. Objective: Although tremendous efforts have been made to link biological indicators to the progression of AD, limited attention has been paid to investigate the multi-factorial role of socioeconomic status (SES) in the prevalence or incidence of AD. There is high demand to explore the synergetic effect of sex and SES factors in moderating the neurodegeneration process caused by the accumulation of A and T biomarkers. Methods: We carry out a meta-data analysis on the longitudinal neuroimaging data, clinical outcomes, genotypes, and demographic data in Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). Results: Our major findings include 1) education and occupation show resilience effects at the angular gyrus, superior parietal lobule, lateral occipital-temporal sulcus, and posterior transverse collateral sulcus where we found significant slowdown of neurodegeneration due to higher education level or more advanced occupation rank; 2) A and T biomarkers manifest different spatial patterns of brain resilience; 3) BDNF (brain-derived neurotrophic factor) single nucleotide polymorphism (SNP) rs10835211 shows strong association to the identified resilience effect; 4) the identified resilience effect is associated with the clinical manifestation in memory, learning, and organization performance. Conclusion: Several brain regions manifest resilience from SES to A and T biomarkers. BDNF SNPs have a potential association with the resilience effect from SES. In addition, cognitive measures of learning and memory demonstrate the resilience effect.

Amyloid β peptides in plasma in early diagnosis of Alzheimer's disease: A multicenter study with multiplexing

2010 ◽  
Vol 223 (2) ◽  
pp. 366-370 ◽  
Author(s):  
P. Lewczuk ◽  
J. Kornhuber ◽  
E. Vanmechelen ◽  
O. Peters ◽  
I. Heuser ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Multicenter Study ◽  
Amyloid Β

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

2019 ◽  
Vol 70 (4) ◽  
pp. 1275-1286 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Randy J. Kulesza ◽  
Yusra Mansour ◽  
Mario Aiello-Mora ◽  
Partha S. Mukherjee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Auditory System ◽  
Auditory Pathway ◽  
Central Auditory System

scholarly journals Synthesis aided structural determination of amyloid-β(1–15) glycopeptides, new biomarkers for Alzheimer's disease

2014 ◽  
Vol 50 (95) ◽  
pp. 15067-15070 ◽  
Author(s):  
Peng Wang ◽  
Jonas Nilsson ◽  
Gunnar Brinkmalm ◽  
Göran Larson ◽  
Xuefei Huang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Amyloid Β ◽  
Structural Determination ◽  
Potential Biomarker ◽  
New Biomarkers

The structure of an Aβ glycopeptide is determined, which is a potential biomarker for early diagnosis of Alzheimer's disease.

scholarly journals Temporal Lobe Epilepsy and Alzheimer’s Disease: From Preclinical to Clinical Evidence of a Strong Association

2021 ◽  
pp. 1-19
Author(s):  
Mario Tombini ◽  
Giovanni Assenza ◽  
Lorenzo Ricci ◽  
Jacopo Lanzone ◽  
Marilisa Boscarino ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Detrimental Effect ◽  
Clinical Evidence ◽  
Epileptiform Activity ◽  
Strong Association ◽  
Amyloid Β ◽  
Neurodegenerative Process

Increasing evidence coming from both experimental and humans’ studies strongly suggest the existence of a link between epilepsy, in particular temporal lobe epilepsy (TLE), and Alzheimer’s disease (AD). Patients with mild cognitive impairment and AD are more prone to have seizures, and seizures seem to facilitate amyloid-β and tau deposits, thus promoting neurodegenerative processes. Consistent with this view, long-lasting drug-resistant TLE and AD have been shown to share several pathological and neuroimaging features. Even if studies addressing prevalence of interictal and subclinical epileptiform activity in these patients are not yet conclusive, their findings raise the possibility that epileptiform activity might negatively impact memory and hasten cognitive decline, either directly or by association with unrecognized silent seizures. In addition, data about detrimental effect of network hyperexcitability in temporal regions in the premorbid and early stages ofADopen up newtherapeutic opportunities for antiseizure medications and/or antiepileptic strategies that might complement or enhance existing therapies, and potentially modify disease progression. Here we provide a review of evidence linking epileptiform activity, network hyperexcitability, and AD, and their role promoting and accelerating neurodegenerative process. Finally, the effects of antiseizure medications on cognition and their optimal administration in patients with AD are summarized.

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