Neuroinflammation, Hyperphosphorylated Tau, Diffuse Amyloid Plaques, and Down-Regulation of the Cellular Prion Protein in Air Pollution Exposed Children and Young Adults

Air pollution exposures have been linked to neuroinflammation and neuropathology. Autopsy samples of the frontal cortex from control (n ) 8) and pollution-exposed (n ) 35) children and young adults were analysed by RT-PCR (n ) 43) and microarray analysis (n ) 12) for gene expression changes in oxidative stress, DNA damage signalling, NF?B signalling, inflammation, and neurodegeneration pathways. The effect of apolipoprotein E (APOE) genotype on the presence of protein aggregates associated with Alzheimer’s disease (AD) pathology was also explored. Exposed urbanites displayed differential (>2-fold) regulation of 134 genes. Forty percent exhibited tau hyperphosphorylation with pre-tangle material and 51% had amyloid-â (Aâ) diffuse plaques compared with 0% in controls. APOE4 carriers had greater hyperphosphorylated tau and diffuse Aâ plaques vs. E3 carriers (Q ) 7.82, p ) 0.005). Upregulated gene network clusters included IL1, NF?B, TNF, IFN, and TLRs. A 15-fold frontal down-regulation of the prion-related protein (PrPC) was seen in highly exposed subjects. The down-regulation of the PrPC is critical given its important roles for neuroprotection, neurodegeneration, and mood disorder states. Elevation of indexes of neuroinflammation and oxidative stress, downregulation of the PrPC and AD-associated pathology are present in young megacity residents. The inducible regulation of gene expression suggests they are evolving different mechanisms in an attempt to cope with the constant state of inflammation and oxidative stress related to their environmental exposures. The authors concluded that these findings support a role for air pollution in CNS damage and its impact upon the developing brain and the potential aetiology of AD and mood disorders.

Authors: Calderon-Garciduenas, Lilian; Kavanaugh, Michael; Block, Michelle; D’Angiulli, Amedeo; Delgado-Chavez, Ricardo; Torres-Jardon, Ricardo; Gonzalez-Maciel, Angelica; Reynoso-Robles, Rafael; Osnaya, Norma; Villarreal-Calderon, Rodolfo; Guo, Ruixin; Hua, Zhaowei; Zhu, Hongtu; Perry, George; Diaz, Philippe ;Full Source: Journal of Alzheimer’s Disease 2012, 28(1), 93-107 (Eng) ;