Air pollution, dementia, and lifespan in the socio-economic gradient of aging: perspective on human aging for planning future experimental studies

Finch, Caleb E.

doi:10.3389/fragi.2023.1273303

Cited by 3 publications

(1 citation statement)

References 69 publications

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“…While the primary focus of many studies has been on identifying biomarkers derived from EVs for differential diagnosis, there is a dire need to assess other metrics. These include prognostic insights, tracking disease progression, monitoring treatment responses, screening for risk, stratifying participants in clinical trials, interpreting drugs pharmacokinetics and pharmacodynamics and identifying responses to environmental toxins [232][233][234][235].…”

Section: Extending the Approach Beyond The Differential Diagnosismentioning

confidence: 99%

Extracellular Vesicles for Alzheimer’s Disease and Dementia Diagnosis

Taha

2024

Preprint

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Accurate differential diagnosis of dementia disorders including Alzheimer’s disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD), and vascular cognitive impairment and dementia (VCID), along with conditions like prodromal mild cognitive impairment (MCI) or negative controls (NCs), continues to challenge neurologists. The nuanced and sometimes shared pathophysiological features underscore the need for precision in developing disease-modifying therapies. In the pursuit of reliable antemortem biomarkers, extracellular vesicles (EVs) have emerged as a popular tool for their capacity to encapsulate disease-specific signatures, particularly in neurodegenerative and neurological disorders. To this end, we have performed a comprehensive, PRISMA-guided systematic review and meta-analysis, utilizing sophisticated statistical modeling to determine the diagnostic accuracy, explore between-study variance and heterogeneity (I2), and investigate potential publication bias using various statistical tests.Biomarkers derived from general EVs demonstrated superior diagnostic accuracy, less between-study variance, heterogeneity, and publication bias than those from speculative CNS-enriched EVs. The trim-and-fill method suggested a potential overestimation of diagnostic effectiveness for biomarkers derived from CNS-enriched EVs due to four hypothesized missing studies with low diagnostic results, but none for general EVs. Meta-regressions revealed that studies using cerebrospinal fluid or serum, involving non-fasting individuals, sampling in the afternoon, employing citrate instead of EDTA for blood collection, using thrombin for coagulation factor depletion, isolating EVs with purer methods such as combined ultracentrifugation and size-exclusion chromatography, not freezing EVs post-isolation, and quantifying miRNA biomarkers, achieved better diagnostic accuracy and less heterogeneity. The diagnostic accuracy was low in differentiating among different dementia disorders. However, the analysis for diagnosing persons with AD vs. VCID achieved the highest diagnostic accuracy, suggesting that further studies may focus on this comparison. Additionally, we highlight several limitations in the included studies and recommend the following: Implement the use of appropriate negative controls, thorough documentation of preanalytical factors, inclusion of more dementia groups beyond AD, comprehensive reporting on pharmacological treatments, consideration of racial and ethnic minority groups, adherence to ISEV guidelines, application of the A-T-N framework, detailed documentation of dementia stages, extension of studies beyond differential diagnosis, reanalysis when postmortem definitive diagnostics become available, evaluation of prodromal conversion rates, and commitment to accurate statistical modeling and data transparency. We hope that lessons learned from this comprehensive meta-analysis can be beneficial for those attempting to discover biomarkers for AD and related dementias through EVs or alternative approaches.

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Section: Extending the Approach Beyond The Differential Diagnosismentioning

confidence: 99%

Extracellular Vesicles for Alzheimer’s Disease and Dementia Diagnosis

Taha

2024

Preprint

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Inhaled Pollutants of the Gero-Exposome and Later-Life Health

Finch,

Thorwald

2024

The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences

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Inhaled air pollutants (AirP) comprise extraordinarily diverse particles, volatiles, and gases from traffic, wildfire, cigarette smoke, dust, and various other sources. These pollutants contain numerous toxic components which collectively differ in relative levels of components, but broadly share chemical classes. Exposure and health outcomes from AirP are complex, depending on pollutant source, duration of exposure, and socioeconomic status. We discuss examples in the current literature on organ responses to AirP, with a focus on lung, arteries, and brain. Some transcriptional responses are shared. It is well accepted that AirP contributes to Alzheimer’s disease and other neurodegenerative conditions in the Gero-Exposome. However, we do not know which chemical compounds initiate these changes and how activation of these transcriptional pathways is further modified by genetics and prenatal development.

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Traffic-related air pollution and APOE4 can synergistically affect hippocampal volume in older women: new findings from UK Biobank

Popov,

Ukraintseva,

Duan

et al. 2024

Front. Dement.

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A growing research body supports the connection between neurodegenerative disorders, including Alzheimer's disease (AD), and traffic-related air pollution (TRAP). However, the underlying mechanisms are not well understood. A deeper investigation of TRAP effects on hippocampal volume (HV), a major biomarker of neurodegeneration, may help clarify these mechanisms. Here, we explored TRAP associations with the HV in older participants of the UK Biobank (UKB), taking into account the presence of APOE e4 allele (APOE4), the strongest genetic risk factor for AD. Exposure to TRAP was approximated by the distance of the participant's main residence to the nearest major road (DNMR). The left/right HV was measured by magnetic resonance imaging (MRI) in cubic millimeters (mm3). Analysis of variance (ANOVA), Welch test, and regression were used to examine statistical significance. We found significant interactions between DNMR and APOE4 that influenced HV. Specifically, DNMR <50m (equivalent of a chronically high exposure to TRAP), and carrying APOE4 were synergistically associated with a significant (P = 0.01) reduction in the right HV by about 2.5% in women aged 60–75 years (results for men didn't reach a statistical significance). Results of our study suggest that TRAP and APOE4 jointly promote neurodegeneration in women. Living farther from major roads may help reduce the risks of neurodegenerative disorders, including AD, in female APOE4 carriers.

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Air pollution, dementia, and lifespan in the socio-economic gradient of aging: perspective on human aging for planning future experimental studies

Cited by 3 publications

References 69 publications

Extracellular Vesicles for Alzheimer’s Disease and Dementia Diagnosis

Extracellular Vesicles for Alzheimer’s Disease and Dementia Diagnosis

Inhaled Pollutants of the Gero-Exposome and Later-Life Health

Traffic-related air pollution and APOE4 can synergistically affect hippocampal volume in older women: new findings from UK Biobank

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