What is Inflammatory Alzheimer's Disease?

Chronic inflammation is at the crux of many modern diseases. Therefore, it should come as no surprise that inflammation plays a major role in the development of Alzheimer’s disease. In fact, there is an entire subtype of Alzheimer’s disease dedicated to inflammation.

So, what is inflammatory Alzheimer’s? Inflammatory Alzheimer’s is the first subtype of Alzheimer’s disease that is characterized by the presence of chronic inflammation in the body and the brain. This subtype is most closely correlated with a positive ApoE4 status and inflammatory markers in the blood.

What Causes Inflammatory Alzheimer’s

Inflammation is a complex and essential process that occurs in all healthy individuals. Essentially, inflammation is the way that our bodies defend themselves against threats like infections, injuries, and toxins. So, why would a healthy and normal process cause a disease as terrible as Alzheimer’s disease? In some cases, the body begins to become more pro-inflammatory than anti-inflammatory. This is referred to as chronic inflammation. When this occurs in the brain along with cognitive impairment, it is known as inflammatory Alzheimer’s disease [1].

Inflammatory Alzheimer’s disease occurs in three steps [2]:

1. For inflammatory Alzheimer’s to exist, there must first be inflammation. There is no single source of inflammation for all inflammatory Alzheimer’s cases, but there are some individuals who are prone to developing chronic inflammation. Of note, the ApoE4 genotype makes an individual more sensitive to developing inflammation and cognitive decline. 
2. Once inflammation becomes chronic, the brain begins to react. The brain perceives the inflammation as a threat and begins to produce amyloid plaque and tau tangles. These are a natural defense system to kill microbes and protect the brain. However, there is no actual infection in this case, and these products begin to build up and destroy brain tissues. Since chronic inflammation is still present, the brain continues to pump out these proteins despite their deleterious effects.
3. Eventually, the brain’s resident immune cells, called the microglia, realize that there is a ton of inflammation and protein buildup in their jurisdiction and become “activated”. The activated microglia attempt to remove the amyloid plaque and tau tangles, but inevitably become overburdened and call for backup. They do this by releasing pro-inflammatory signaling molecules called cytokines that tell nearby microglial cells to come and help. Unfortunately, this just adds to the total inflammation of the brain and results in the production of more amyloid plaque and tau tangles. Herein, a vicious cycle is formed and inflammatory Alzheimer’s is established. So, while inflammation is not a singular thing that causes Alzheimer’s disease, it is what sets the tempo by which all other processes are able to degrade the brain. 

Signs and Symptoms of Inflammatory Alzheimer’s

Since inflammation is different from one person to the next, not all people will experience symptoms in the same way. However, we have outlined the most common signs and symptoms of inflammatory Alzheimer’s below [1].

• Inflammatory Alzheimer’s is correlated with those who have one or two copies of the ApoE4 allele
• It is common for people to have a difficult time storing new information
• • This typically occurs in the late fifties to sixties for those with two ApoE4 copies.
  • For those with one or no copies of ApoE4, this typically occurs in the sixties or seventies
• A decline in the volume of the hippocampus

Biochemical markers of inflammatory Alzheimer’s:

• High C-reactive protein (CRP)
• • Values should be below 0.9 mg/L
• Low albumin to globulin ratio
• • Values should be 1.8:1 or grater
• High interleukin-6 (IL-6)
• • Values should be less than 3 pg/mL
• High tumor necrosis factor (TNFa)
• • Values should be less than 6.0 pg/mL
• Insulin resistance is another common finding

Treatment of Inflammatory Alzheimer’s 

When treating inflammatory Alzheimer’s, the best intervention is to remove systemic inflammation. This requires a combination of dietary and lifestyle changes alongside targeted supplementation.

Step 1 is to remove inflammatory foods. While it is important to meet with a dietitian to establish which foods are inflammatory for you, there are some foods that tend to be inflammatory in people:

• Omega-6 fats: These fats are an essential part of a healthy, balanced diet. That being said, most Americans tend to get too many. As a result, the body becomes much more susceptible to inflammation. Omega-6 rich foods include oils like soybean, canola, peanut, corn, and sunflower oil [3].
• Sugar: Although it is a staple of the American diet and in many delicious foods, sugar is incredibly inflammatory and can contribute to the progression of inflammatory Alzheimer’s [4]. Opt for foods low in added sugars. 
• Dairy: This is another favorite across America and much of Europe. However, dairy is one of the most common allergens across the world. In fact, dairy even causes inflammation in people who aren’t allergic to dairy. Swap dairy for less inflammatory milks like almond, soy, or A2 cow’s milk if not lactose intolerant [5].

Step 2 is to add in anti-inflammatory foods. While it is important to remove dietary sources of inflammation, it is equally important to introduce foods that can help lower inflammation on the spot. Some of the best anti-inflammatory foods are:

• Omega-3 fats: Unlike omega-6 fats, most Americans do not consume enough omega-3 fats. Omega-3 fats are an important part of our bodies’ natural way to decrease inflammation in the blood and brain. Sources of omega-3 fats include salmon, mackerel, anchovies, sardines, herring, chia seeds, flax seeds, and walnuts [2].
• Antioxidants: If you have ever heard the phrase “eat the rainbow”, this is why. Vibrantly colored foods are rich in antioxidants. These antioxidants travel throughout the body and clean up molecules that are causing DNA damage and inflammation. 
• Probiotic foods: Inflammation often begins in the gut. Probiotic foods help to restore our microbiome and can regulate inflammation this way. Good sources of probiotics are kombucha, kefir, kimchi, and sauerkraut.

Step 3 is to address lifestyle. The two most important things here are to reduce stress and improve sleep.

• Stress itself causes inflammation and can play a role in the progression of diseases like inflammatory Alzheimer’s [6]. To reduce stress, it can be helpful to practice meditation, yoga, or even just slowing down to read a book before bed. If stress levels are a big problem, it can be incredibly important to get help from a doctor or therapist.
• Sleep is our bodies’ chance to unwind from the day, reduce stress, lower inflammation, and literally clear plaques from the brain [7]. For this reason, getting quality sleep is one of the most important things you can do to prevent disease. To get good sleep, it is important to stick to a consistent schedule and limit screen time leading to bedtime. 

Conclusion

Inflammatory Alzheimer’s is a complex condition that is different from one person to another. Every treatment plan is going to depend on the individual and should be managed by a professional. If you are worried that you might be at risk of inflammatory Alzheimer’s, it is important to work with a doctor and dietitian who are trained in the Bredesen Protocol and have experience with a functional approach to treating cognitive decline. Contact the Amos Institute today to make an appointment with a dietitian trained in the Bredesen Protocol and functional medicine.

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References:

1. Bredesen, D. E. (2017). The end of Alzheimer's: The first program to prevent and reverse cognitive decline. Avery, an imprint of Penguin Random House. 
2. Kinney et al., 2018: 10.1016/j.trci.2018.06.014
3. Blasbalg et al., 2011: 10.3945/ajcn.110.006643
4. Corte et al., 2018: 10.3390/nu10050606
5. Jianqin et al., 10.1186/s12937-016-0147-z
6. Wirtz & Känel, 2019: 10.1007/s11886-017-0919-x
7. Jessen et al., 2015: 10.1007/s11064-015-1581-6