Severe air pollution exposures produce systemic, respiratory, myocardial, and brain inflammation and Alzheimer’s disease (AD) hallmarks in clinically healthy children. We tested whether hippocampal metabolite ratios are associated with contrasting levels of air pollution, APOE and BMI in paired healthy children and one parent sharing the same APOE alleles. We used (1) H-MRS to interrogate bilateral hippocampal single-voxel in 57 children (12.45± 3.4 years) and their 48 parents (37.5± 6.78 years) low pollution city v Mexico City (MC). NAA/Cr, Cho/Cr, and mI/Cr metabolite ratios were analysed. The right hippocampus N-acetylaspartate/creatine (NAA/Cr) was significantly different between cohorts (p=0.007). The NAA/Cr ratio in right hippocampus: controls v APOE 4 MC children and left hippocampus: MC APOE 4 parents v their children was significantly different after adjusting for age, gender and BMI (p=0.027 and 0.01, respectively). The NAA/Cr ratio is considered reflective of neuronal density/functional integrity /loss of synapses/higher pTau burden, thus a significant decrease in hippocampal NAA/Cr ratios may constitute a spectral marker of early neurodegeneration in young urbanites. Decreases in NAA/Cr correlate well with cognitive function, behavioural symptoms and dementia severity, thus since the progression of AD starts decades before clinical diagnosis, our findings support the hypothesis that under chronic exposures to fine particulate matter and ozone above the standards, neurodegenerative processes start in childhood and APOE 4 carriers are at higher risk. Gene /environmental factors are critical in the development of Alzheimer's disease and the identification and neuroprotection of young urbanites at high risk must become a public health priority.
This is an author-produced, peer-reviewed version of this article. The final, definitive version of this document can be found online at Journal of Alzheimer’s Disease, published by IOS Press. Copyright restrictions may apply. doi: 10.3233/JAD-150415
Mukherjee, Partha S.. (2015). "A Critical Proton MR Spectroscopy Marker of Alzheimer Early Neurodegenerative Change: Low Hippocampal NAA/Cr Ratio Impacts APOE 4 Mexico City Children and Their Parents.". Journal of Alzheimer's Disease, 48(4), 1065-1075. http://dx.doi.org/10.3233/JAD-150415