Research Article
CSF Biomarkers: Low Amyloid-β 1-42 and BDNF and High IFN γ Differentiate Children Exposed to Mexico City High Air Pollution V Controls. Alzheimer's Disease Uncertainties
Lilian Calderón-Garcidueñas1,2*, Chih-kai Chao1, Charles Thompson1, Joel Rodríguez-Díaz2, Maricela Franco-Lira3, Partha S. Mukherjee4 and George Perry5
1The Center for Structural and Functional Neurosciences, University of Montana, Missoula, MT, USA
2Escuela de Ciencias de la Salud, Universidad del Valle de México, Saltillo, Coahuila, 25204, México
3Hospital Central Militar, Mexico City, Mexico
4Department of Mathematics, Boise State University, Boise, Idaho, USA
5College of Sciences, University of Texas at San Antonio, Texas, USA
- Corresponding Author:
- Lilian Calderón-Garcidueñas
The Center for Structural and Functional Neurosciences
University of Montana,32 Campus Drive
287 Skaggs Building, Missoula, USA
Tel: 406-243-4785
Fax: 406-243-5228
E-mail: lilian.calderon-garciduenas@umontana.edu
Received date: April 17, 2015; Accepted date: May 13, 2015; Published date: May 20, 2015
Citation: Calderón-Garcidueñas L, Chao CK, Thompson C, Rodríguez-Díaz J, Franco-Lira M, et al. (2015) CSF Biomarkers: Low Amyloid-β1-42 and BDNF and High IFN γ Differentiate Children Exposed to Mexico City High Air Pollution V Controls. Alzheimer’sDisease Uncertainties. J Alzheimers Dis Parkinsonism 5:189. doi:10.4172/2161-0460.1000189
Copyright: © 2015 Calderón-Garcidueñas L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: Long-term exposure to fine particulate matter (PM2.5) and ozone above US EPA standards is associated with increased risk of Alzheimer’s disease (AD). Mexico City Metropolitan Area (MCMA) children have prenatal and lifelong exposures to high PM2.5 and O3. MCMA children and young adults exhibit frontal tau hyperphosphorylation (40%) and amyloid-β diffuse plaques (51%) and a brain imbalance in genes involved in oxidative stress, inflammation, innate and adaptive immune responses. Methods: We measured total tau, tau phosphorylated at threonine 181, amyloid-β1-42 (Fujirebio,US), brain derived neurotrophic factor (BDNF), inflammatory mediators, insulin, and leptin in normal CSF samples from 56 MCMA and 26 control children age 11.9 ± 4.7 years. Results: Aβ 1-42 concentrations were lower in MCMA children (p=0.001) and correlated with cumulative PM2.5 (R2= 0.70). MCMA children had low BDNF (p=0.02) and high IFN-γ (p=0.0003) versus controls. In MCMA children, leptin correlated with insulin and MCP-1 (rs 0.34 and 0.41). Conclusion: Low Aβ1-42 in normal CSF samples from megacity children is a major finding given the interpretation of Aβ 1-42 in the temporal evolution of AD biomarkers. Low CSF Aβ, high IFN γ -detected in early AD and a key neuroinflammatory mediator in AD models-, and low BDNF strongly suggest deleterious CSF changes are evolving in 12 y olds, historically showing deficits in attention and short-term memory, information processing speed and executive function, plus olfactory, auditory and metabolic brain changes. Consideration for a shift in the preclinical AD paradigm is put forward in the setting of severe air pollution exposures. CSF children’s derangements involving Aβ 1-42, BDNF and IFN-γ and the potential discontinuity in the leptin central signaling pathway could be signifying a vicious downward spiral towards AD. We need to aim our efforts to the identification and mitigation of environmental factors influencing Alzheimer’s disease.
