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

Abstract

Background: Over 20 genetic risk factors have been confirmed to 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. Methods: Based on reports associating various inhalants with AD 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. Results: Mice exposed to air pollution showed 72-129% increases in brain levels of both amyloid-β peptides Aβ40 and Aβ42, as well as Aβ42/40 (p <0.01). Conclusions: These effects on elevation of brain Aβ exceed those 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.

Exposure to air pollution and cognitive impairment risk: a meta-analysis of longitudinal cohort studies with dose-response analysis

“…Importantly, microglial activation has been implicated in the progression of diseases such as dementia [39]. Third, the olfactory bulb is another pathway [40] through which PM enters the body, reaching the brain directly and inducing a series of changes such as increased the level of amyloid-β42, hyperphosphorylated τ, and neural degeneration [41,42].…”

Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease

“…Furthermore, children from the MCMA have increased serum autoantibodies against neuronal proteins, likely due to compromised brain immunity and BBB breakdown [153]. In mouse experimental studies, aerosolized nickel nanoparticles caused a rapid and drastic increase in Aβ40 and Aβ42 [154]. Also, APOE null mice exposed to mixed vehicle exhaust have accelerated BBB breakdown, decreased expression of tight junction proteins (e.g., occludin, claudin-5) and increased generation of reactive oxygen species activity [155].…”

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].…”