Rapid doubling of Alzheimer’s amyloid-β40 and 42 levels in brains of mice exposed to a nickel nanoparticle model of air pollution

Abstract

Over 20 genetic risk factors have been confirmed to Background: associate with elevated risk for Alzheimer's disease (AD), but the identification of environmental and/or acquired risk factors has been more elusive. At present, recognized acquired risks for AD include traumatic brain injury, hypercholesterolemia, obesity, hypertension, and type 2 diabetes. Based on reports associating various inhalants with AD Methods: pathology, we investigated the possibility that air pollution might contribute to AD risk by exposing wild-type mice to a standard air pollution modeling system employing nickel nanoparticle-enriched atmosphere for 3 hr. Mice exposed to air pollution showed 72-129% increases in brain Results: levels of both amyloid-β peptides Aβ40 and Aβ42, as well as Aβ42/40 (p <0.01). These effects on elevation of brain Aβ exceed those Conclusions: associated with trisomy 21, a known risk for early onset AD pathology, raising the possibility that clinical importance might be attached. Further work is required to establish the molecular and physiological basis for these phenomena. The rapid, dramatic effect, if verified, would suggest that inhalant exposures should be evaluated for their possible roles in contributing to the environmental risk for common forms of AD.

The emerging risk of exposure to air pollution on cognitive decline and Alzheimer's disease – Evidence from epidemiological and animal studies

“…These findings demonstrate pathological changes that may explain the link between APOE ε4 carrier status and increased risk for cognitive impairment seen in epidemiological studies [12] , [74] , [89] . Since exacerbation of Aβ load has also been shown in wild type mice as described above [17] , [110] , [111] , determining whether PM acts through AD specific pathways in addition to inflammation response and ROS generation requires further study.…”

“… Morgan et al., 2011 [15] 2012 FVBN mice Nickle Nanoparticles M,F 8 1 time exposure 3 h 1000 2 Aβ load increased. Kim et al., 2012 [111] 2013 C57BL/6J mice UF PM collected in the Cambridge, MA area M,F 1 PND 4–7, 10–13, 56–60. 4 h/day 96 2.5 test Increased fixed ration operant wait time, no change in locomotor behaviors.…”

“…Increased levels of Aβ 42 and phosphorylated tau in multiple brain regions are also observed in the highest exposure group (∼1 mg/m 3 ) [110] . Mice exposed to a similar concentration of nickel nanoparticles also exhibit an increased Aβ 42 load [111] , suggesting that the effect on Aβ buildup in the brain may be, in part, due to the concentration of particulates exposed, rather than the its chemical constituents. Exposure to diesel exhaust has also been shown to negatively affect performance of seven week old mice in the Morris Water Maze task [112] .…”

Role of Environmental Contaminants in the Etiology of Alzheimer&#8217;s Disease: A Review

“…Researchers have examined whether toxic metals including nickel, vanadium, lead and certain gases such as CO, NO x , and SO 2 present in polluted air may cause reactive oxygen species (ROS) production, oxidative stress, chronic neuroinflammation, cerebrovascular damage, Aβ peptide accumulation, and neuron damage/loss contributing to AD pathogenesis [ 173 ]. AD associated amyloid-β40 and amyloid-β42 levels were increased in mice brains of mice exposed to a nickel nanoparticle model of air pollution [ 174 ]. In Mexico City, children exposed to severely polluted environments demonstrated neuronal accumulation of misfolded proteins similar to the anatomy observed in the early stages of both AD and Parkinson’s disease [ 12 ].…”

Incidence of mild cognitive impairment in World Trade Center responders: Long‐term consequences of re‐experiencing the events on 9/11/2001

“…Chronic PTSD is a disorder commonly characterized by the stressful re‐experiencing of a traumatic event accompanied by a chronically dysregulated stress‐response [5,6] that has been associated with cognitive dysfunction [7], changes in neural responses [8], increased neuropathology [9], reduced hippocampal volume [10], and cortical thinning [11]. Long‐term exposure to airborne pollutants has been associated with increased neuropathology [12,13], dopaminergic changes [14], and incidence of Alzheimer's disease [15].…”