The Link Between Inflammation and Alzheimer’s Disease

by Jordan Taffet, Dietetic Intern, M.S. Candidate

Inflammation refers to the body’s immune response to a disruption in homeostasis. Think about the last time you cut yourself. The site became red and hot, and eventually the wound clotted and healed. This was acute inflammation at its best. The inflammation did its job to heal the wound and then dissipated. Unfortunately, for a number of reasons, this inflammatory process can become impaired, creating chronic, systemic inflammation, which directly contributes to disease pathology. There are many different causes and types of inflammation, but the one most relevant for cognitive functioning is neuroinflammation. Neuroinflammation is an inflammatory response within the brain or spinal cord that can lead to neurodegenerative diseases like Alzheimer’s Disease. Because of the inflammation that occurs within the brain, mediators such as cytokines, chemokines and reactive oxygen species are released in the brain and spinal cord to mitigate the inflammatory processes (1). Neuroinflammation is important surrounding the discussion of cognitive functioning, as neuroinflammation is directly related to a decline in cognitive functioning and, as a result, the development of neurodegenerative diseases.

Factors contributing to inflammation

Neuroinflammation and inflammatory processes in the body can be caused by several factors, one of which is stress. Current research suggests that chronic exposure to stressors directly contributes to chronic inflammation, a major problem, since our modern lifestyle creates massive psychological and physiological stress. The impact of stress on inflammation is due to the fact that constant exposure to stressors may impair neuroplasticity, the brain’s ability to grow, change, and heal, due to activation of microglial cells, which may enhance overall neuroinflammation (1). This type of inflammatory cascade is one of the culprits responsible for the development of Alzheimer’s Disease. The systemic inflammation creates acute lesions and causes microglial cells to morph in their shape and form, increasing the synthesis of pro- inflammatory cytokines, which results in the symptoms ultimately seen in people with neurodegenerative diseases (2). Stressors that initiate inflammatory processes are also found through environmental exposures, such as traumatic brain injuries and systemic infection. Environmental exposures that lead to chronic inflammation have been shown to provide the groundwork for the development of Alzheimer’s Disease through the activation of the immune system by infection (3).

Other contributors to chronic neuroinflammation are aging and one’s predisposition to certain genetic mutations. It is understood that one of the strongest factors for developing Alzheimer’s Disease is the presence of the APOE4 gene. This is due to APOE4’s role in metabolizing cholesterol, activating and producing neurotoxins of microglial cells, and increasing one’s risk of central nervous system and systemic infections (2). While the presence of this gene does not suggest a definite Alzheimer’s diagnosis, the APOE4 genetic mutation combined with the process of aging, has been shown to increase one’s risk for developing Alzheimer’s Disease. This is because aging in general contributes to cognitive decline through the natural decline in immunity and T helper 2 response that occurs. This creates a process known as “inflammaging”, which is an increase in the imbalance between inflammatory and anti-inflammatory pathways as we age (2). As we age, our likelihood for developing many diseases increases, as well as our likelihood for developing overall cognitive decline.

A third contributor to inflammation is nutrition. Several studies highlight the role that obesity plays in contributing to overall inflammation and cognitive decline. Because obesity results in systemic and central inflammation, there is an increase in the induction of cytokines produced, which have been directly correlated to cognitive decline (4). This is due to the fact that excess adipose tissue triggers the release of radical oxygen species and pro-inflammatory cytokines, like TNF-alpha and interleukin-6 (IL-6) (5). The long-term state of maladaptive responsiveness to inflammation that obesity causes can ultimately lead to inflammation-induced insulin resistance, also known as Type III Diabetes, or Alzheimer’s Disease (6). Generally speaking, maintaining a healthy body weight and focusing on a nourishing diet is protective of cognitive decline. Research shows that following a Mediterranean diet has been shown to be protective of inflammation, as it emphasizes consumption of antioxidants and omega-3 fatty acids, shown to lower inflammatory markers, such as C-reactive protein (CRP) and Interleukin-6 (IL-6) (7).

How we assess inflammation – benefits and limitations of inflammatory markers

Because the connection between inflammation and disease is so well established, assessing inflammatory status is often a central part of a patient’s medical work up. Currently, inflammation is assessed through the use of biomarkers including: MHC Class II, CRP, cox-2, MCP-1, TNF-alpha, IL-6, and IL-1-beta (3). The biomarkers most often used are CRP, TNF- alpha, and IL-6. By looking at these biomarkers in the blood, one can generally determine their state of inflammation. These biomarkers are important for neurodegenerative diseases, as research indicates that CRP and IL-6 have been shown to be elevated for up to five years before a clinical diagnosis of dementia can be made (2). The benefit of these biomarkers is that they can be easily monitored and determined through a simple blood test. However, research indicates that many individuals have acquired too much damage through chronic inflammation by the time these biomarkers are assessed, and that, because of this, a new system for measuring and monitoring inflammation is needed. Ultimately, measuring these individual biomarkers alone is not enough for preventing against the damage of inflammation. However, further research is needed to discover additional biomarkers and to create a new system for measuring and monitoring inflammation (8).

Indirect inflammatory markers, such as oxidized LDL can also be used for assessing inflammation. Research indicates that higher levels of oxidative stress are associated with neurodegeneration and higher levels of oxidized LDL. Oxidized LDL damages neuronal cells, inducing DNA fragmentation and cell lysis (9). However, research indicates that one can fight against high levels of oxidized LDL through increasing flavonoids within the diet (9).

Minimizing inflammation and preventing cognitive decline

Overall, inflammation is a natural process that occurs ultimately to protect the body. However, chronic inflammation that goes untreated can be incredibly damaging for the body and mind. It is important to understand how the body reacts to inflammation and to take action if you are at risk for neurodegenerative diseases. Through proper treatment and monitoring, neuroinflammation can be minimized to protect and prevent against the development of neurodegenerative diseases.

References:

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