Alzheimer’s disease (AD) is a progressive neurodegenerative disease that involves gradual cognitive decline. About 13% of people over 65 years old have Alzheimer’s disease and nearly 45% of people over the age of 85 have it. (Source) Much evidence points to an imbalance in production and clearance of beta amyloid plaque in the brain. These toxic plaques injure neurons and lead to dementia and memory problems. The toxicity of amyloid depends on phosphorylated proteins called Tau. We now know there may be other triggers to amyloid production including toxic exposure and infections. Some of these include borrelia, herpes simplex type 1 and 2, chlamydia pneumonia, h. pylori and others. Early onset Alzheimer’s disease typically occurs in patients less than 65 years old and may be related to gene mutations in APP, presenilin 1 and presenilin 2. However, the majority of Alzheimer’s cases still occur in patients over 65 years old, commonly referred to as late-onset Alzheimer’s disease or LOAD.
So what is ApoE?
ApoE regulates cholesterol by mediating transport from one tissue to another. In peripheral tissues, ApoE is primarily produced by the liver and macrophages and aids in transporting cholesterol. ApoE4 is associated with high cholesterol, heart disease and stroke as well as Alzheimer’s disease. In the brain it is mainly produced by astrocytes and transports cholesterol to neurons, causing abnormal transport of cholesterol in brain. Proper levels of cholesterol and transport of this substance is essential for proper memory. Studies show that ApoE 4 genotypes strongly affect deposition of beta amyloid forming senile plaques and cause cerebral amyloid angiopathy (CAA) where amyloid is deposited in the cerebral blood vessels. Both of these things are classic findings in the brains of those with AD. ApoE4 seems to have pro-inflammatory effect and decreased ability to thwart oxidative stress which could further exacerbate AD pathology.
ApoE 4/4 is a strong risk factor for Alzheimer’s disease
Patients who have ApoE 4/4 have a very strong genetic risk for development of Alzheimer’s disease. This association is weaker among African Americans and Hispanics and stronger in Japanese people compared with Caucasians. ApoE 4/4 is associated with high incidence of AD at a younger age. It is clear that this gene dramatically increases risk of development of AD. The frequency and average age of onset are as follows:
- ApoE 4 two copes – 91% and 68 years of age
- ApoE 4 one copy – 47% and 76 years of age
- ApoE non-carriers – 20% and 84 years of age
ApoE 4/4 is associated with impaired memory performance and increased risk of memory decline in middle-aged (40–59 years) and elderly (60–85 years) people with mild cognitive impairment (MCI). MCI is defined as a noticeable and measurable decline in cognitive abilities, including memory and thinking skills. Someone with MCI is at an increased risk of eventually developing Alzheimer’s disease. Furthermore, recent research demonstrated that, independently of amyloid plaques, this gene triggers inflammatory cascades that cause brain dysfunction, including blood–brain barrier breakdown, leakage of blood-derived toxic proteins into the brain and reduction in the length of small vessels. Similar to “leaky-gut” this has often been called “leaky-brain”.
APOE and traumatic brain injury
Increasing evidence has shown that this gene is associated with worse outcomes following traumatic brain injury (TBI), regardless of the severity of initial injury. One study demonstrated that the outcome of TBI at six months after injury was much worse in ApoE4 carriers. More than one traumatic brain injury is associated with increased risk of AD. The poorer outcomes associated with ApoE4 might relate to its reduced ability to repair and remodel synapses and protect neurons upon injury compared with ApoE3.
Preventive of cognitive decline those with APOE 4 genetics
Dementia is negatively associated with higher education level, more leisure activity and less stress, and lack of cardiovascular risk factors, like healthy diet. Physical exercise was strongly associated with reduced risk compared to sedentary lifestyle. Recommendations if you happen to have ApoE 4 may include a mildly ketogenic diet Mediterranean style diet with focus on plant-based organic foods and coconut oil. In addition there are many antioxidants that may also protect the brain including the following:
- Green Tea (ECGC)
- Coenzyme Q10
Regardless of if you find yourself a carrier of one or more copies of ApoE 4, you can still live a healthy lifestyle and incorporate many things that will decrease your risk of developing AD.
- Apolipoprotein E: far more than a lipid transport protein.
- Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium.
- Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families.
- ApoE and Alzheimer’s Disease, Risk, Mechanisms and Therapy
- The association between APOE genotype and memory dysfunction in subjects with mild cognitive impairment is related to age and Alzheimer pathology.
- Apolipoprotein E controls cerebrovascular integrity via cyclophilin A.