AAM – Air pollution and Alzheimer’s

Air pollution is a proven environmental risk. It is known to be linked to both respiratory diseases and those of the heart and vascular system. However, recently, its association with Alzheimer’s disease (AD) has been suspected and explored in numerous studies.

Image Credit: Melinda Nagy / Shutterstock.com

There are six main types of air pollutants, including ozone (O3), particulate matter (PM), carbon monoxide (CO), various nitrogen oxides (NOx), sulfur dioxide (SO2) and lead. . Even in the United States, more than a hundred million live in areas with polluted air, which can contribute to the increase in the number of people with AD.

Background

AD is a progressive, irreversible neurodegenerative disease, the most common form of dementia in older people. There are tens of millions of people affected around the world.

While age is the best-known risk factor for AD, others include a family member with the disease, a woman, cardiovascular disease, or a head injury. People with less education are at greater risk, as are people with Down’s syndrome, the latter due to Down’s syndrome. This chromosome codes for the amyloid precursor protein (APP), which gives rise to beta-amyloid.

Oxygen reactive species and oxidative stress

The link between AD and air pollution could be oxidative stress – an accumulation of oxidative molecules and oxidized products in the body due to the presence of excessive reactive oxygen species (ROS) that exceed the the body’s natural antioxidant capacity. ROS generation is increased in the body upon exposure to air pollution, and the resulting oxidative stress can impair brain function.

Most of the ROS come from the mitochondrial electronic chain but also from the metabolism of fatty acids within peroxisomes, phagocytic cells during their respiratory burst and several major enzymes. ROSs are essential for immunity because they destroy infectious microbes and keep oxygen levels stable in tissues. They are also involved in the oxidation of cell membranes, proteins and genetic material and are considered fundamental in aging processes.

Aging and oxidative stress

Oxidative stress can underlie aging by damaging key macromolecules, including DNA. Mitochondria are the main source of these molecules called free radicals. They are also primary targets, especially mitochondrial DNA, which naturally carries the brunt of newly generated ROS. It is close to the ROS production site and relatively exposed, with less active repair processes than nuclear DNA.

The cells most affected are the highly differentiated cells that use abundant oxygen for their metabolism, including nerve cells. Aging primarily affects the brain because nerve cells are not known to regenerate or repair themselves. In addition, the brain is rich in fatty acids, a prime target for oxidation, but comparatively lacks antioxidant defenses. As oxidized lipids, proteins and DNA molecules accumulate in the brain, functional deterioration occurs, leading to impaired mental and intellectual abilities.

Characteristics of AD and oxidative stress

AD begins with a slow decline in memory that progresses at varying rates to severe cognitive impairment and loss of independent living skills. The classic lesions of AD in the brain are beta-amyloid plaques and tau neurofibrillary tangles related to the oxidation of macromolecules.

The beta-amyloid peptide (Aβ) may be the cause or the result of the oxidative stress observed in the brains of patients with AD. At the onset of AD, oxidation can cause deposition of this peptide in the brain. The case can be similar for tau tangles.

Alternatively, these can protect the brain from further damage caused by the generation of ROS. Later, however, these molecules could themselves trigger an oxidative inflammatory response, thereby promoting neuronal degeneration and disease progression.

The onset of oxidative stress may, in this scenario, be an early biomarker of AD development even before the onset of telltale plaques and tau entanglements.

In about 90% of AD patients, the sense of smell is impaired early on and predicts cognitive decline with age. This may be due to the loss of olfactory cells and the formation of more neurofibrillary tangles in the olfactory bulb and olfactory centers at the onset of AD.

Oxidative stress seems to occur within the olfactory epithelium, as evidenced by lipid peroxidation, the presence of the abnormal Aβ peptide and the tau protein which constitutes the neurofibrillary tangles. This could be due to air pollutants, which enter the brain through the nasal lining.

Particles and AD

Fine particles in the air, measuring less than 2.5 m (PM2.5) each, can reach the brain by inhalation. They travel through the olfactory epithelium, through olfactory synapses, cross the blood-brain barrier, and interact with other particles from the lungs, for example, and with each other.

These particles cause the release of inflammatory mediators, which activate an immune response against neurons, leading to a state of systemic and respiratory inflammation beyond the antioxidant capacity of the brain. It is a state of oxidative stress.

The result is lipid peroxidation, protein oxidation and the generation of ROS. This leads to the activation of redox-sensitive transcription factors such as NFκB – nuclear factor kappa-light chain-enhancer of activated B cells.

Second, the production of ROS due to these fine particles can directly damage the blood-brain barrier and enhance the production of Aβ. Thus, air pollution causes neuroinflammation and Aβ plaques, which are linked to impaired neuronal function even before the anatomical features of AD appear – plaques and tangles.

Human studies show that people exposed to air pollution are at risk for cognitive impairment and cerebrovascular damage. The risk of dementia was multiplied by 14 among people with the highest annual concentration of air pollution. The shrinkage of the brain was also more pronounced in people exposed to air pollution.

Such pollution is also linked to the presence of tau proteins and Aβ plaques in the frontal cortex. Thus, breathing polluted air over a long period of time can cause oxidative stress, neuroinflammation, degeneration of neurons, formation of Aβ, and thus increase the risk of AD.

Ozone and DA

Chronic exposure to ozone causes brain inflammation, degeneration, vascular alterations, and loss of hippocampal repair pathways and changes in brain plasticity in rat models. These are similar to those seen in patients with AD.

Air pollution can lead to dementia in older women

Conclusion

More research is needed to understand how air pollution causes AD and which mechanistic roads and pathways, especially PM 2.5 and ozone. The synergistic or additive effects of the combined pollutants in the air also merit further study. Reducing and preventing air pollution is an urgent task to prevent the large-scale development of AD and hence the healthcare burden on healthcare professionals worldwide.

The references

Further reading

Comments are closed.