Is there an 'Alzheimer's genotype'?

Is there a genotype for Alzheimer's disease? And if there is, would you want to know your genotype for cognitive decline?

The truth is that there is no single gene that determines your risk; just like there is no one pill that can slow down the onset or even prevent cognitive decline. We also know that you don't just wake up one day with Alzheimer's disease. In fact, research has shown that cognitive decline can start deep in your biochemistry 10 - 25 years before becoming symptomatic. This knowledge has led many neuroscientists, especially Dr. Dale Bredesen and his team at MPI cognitive to ask the RIGHT questions over their 30 years of research into this lifestyle-related, chronic disease. Namely, "what is Alzheimer's disease"; "what causes it" and "what keeps it going". 

Their functional approach to this disease has been revolutionary, and truly life-saving. More than any other disease, a diagnosis of Alzheimer's is devastating as it goes to the very core of our identity - the memory of who we are. Furthermore, it's a disease that breaks the hearts of the person's family as they try to reach the person they love when they themselves don't even remember who they are.

It really is long overdue that we view cognitive decline and Alzheimer's disease as metabolic syndrome, similar to the way we look at CardioMetabolic Syndrome. The ReCODE programme developed by Dr. Breseden aims at achieving exactly that - the reversing and prevention of cognitive decline. As with any syndrome, there is more than one feature of the disease. In the case of cognition, there are over 36 contributing factors. Once these are identified in each person, a personalised plan is developed to start walking the person back towards optimal cognitive health. 

To make things a little easier, ReCODE divides the disease into 5 main subtypes. And this is where we get really excited because it is within this categorisation that we start to observe specific genotypes. And once we can identify a person's unique genetic variations for these key genes, they can start to work upstream; deep into their unique biochemistry to either prevent or reverse cognitive decline. 

Type 1: Inflammatory  - "hot" type

This sub-type is characterised by an inflammatory tone. The genes that are important to determine here are APOE4, IL family, IL6, TNFA, and CRP.

High impact genetic variations in all these genes provide you with a polygenetic view of your risk. We maintain that having these insights is incredibly empowering in preventing cognitive decline as you will be able to personalise your nutrition, environment and lifestyle choices in order to optimise the functioning of these pathways. 

Briefly, an APOE carriers status of E3/E4 predisposes a person to Alzheimer's risk by 30% and the carrier status of E4/E4 as much as 50 -90%.

If you can plot your exome and genome, then it would also be useful to determine your carrier status for other Alzheimer's genes, namely PS1 (presenilin-1) and PS2.

You can order full Exome testing here:

• An increase in C-reactive protein (CRP), which is made by the liver in response to inflammation. Normal Hs-CRP levels should be below 0.9 mg/L
• A decrease in the ratio of albumin to globulin. Normal levels should be at least 1.8:1
• An increase in interleukin-6. Normal levels should be less than 3 pg/ml
• An increase in tumor necrosis factor. TNFa levels should be lower than 6.0 pg/ml.
• Additional metabolic and hormonal abnormalities such as insulin resistance (as we know is commonly seen in diabetes)

If you have this type of genotype, then you would greatly benefit from PreCODE (preventing cognitive decline) by personalising your diet to that of a Ketogenic diet with intermittent fasting, supplementing with high doses of omega 3, PQQ and curcumin together with the right type and amount of exercise, stress transformation and sleep. 

CRP markers and tracking insulin levels are helpful in measuring and tracking your progress. 

This sub-type responds well to ReCODE. 

Type 1.5: Glycotoxic or “Sweet” Alzheimer’s Disease

Type 1 and Type 2 Alzheimer’s Disease can occur together – often seen with neural inflammation in addition to the reduced support for brain synapses. A commonly seen combination of type 1 and type 2 AD is known as Type 1.5 or glycotoxic Alzheimer’s Disease.

Characteristics & Biochemical Markers of Type 1.5

• Although characteristics are similar to those found in Type 1 and Type 2 AD, blood glucose levels and hemoglobin A1c are chronically high in Type 1.5 which results in inflammation.

  • Normal fasting blood glucose levels should be between 70-90 mg/dL.
  • Normal hemoglobin A1c levels should be 4.0-5.3%

• High levels of insulin that is secreted in response to this high blood glucose level leads to insulin resistance. This results in a loss of trophic support.

  • Trophic factors, such as NGF and BDNF, control the development and survival of specific groups of neurons, as mentioned above.
  • Normal fasting insulin levels are 4.0-5.0 μIU/mL.

Type 1, Type 1.5 and Type 2 Alzheimer’s Disease lead to the imbalance between the production and destruction of neural synapses.

Type 2: Atrophic - "cold" type

This sub-type is characterised by a homogeneous APOE4, a later onset by 10 years compared to the inflammatory type, levels of important hormones (thyroid, adrenal, estrogen, progesterone, testosterone, and pregnenolone) are sub-optimal, vitamin D levels are below, insulin levels are too low, and homocysteine levels are too high.

Determining your genotype for APOE4 together with your VDR (Vitamin D-Receptor), IL genes, BDNF, thyroid, detoxification, and methylation genotypes is a great place to start in evaluating your risk. Once you know what your carriers status is for these genes, then you'll know which biochemistry tests to order annually to measure and track your functioning. 

Biochemical Markers of Type 2

• Levels of hormones such as thyroid, adrenal, estrogen, progesterone, testosterone and pregnenolone tend to be suboptimal

• The optimal hormone ranges are:

  • TSH: less than 2.0 mIU/L
  • Free T3: 3.2-4.2 pg/mL
  • Free T4: 1.3-1.8 ng/dL
  • Reverse T3: less than 20 ng/dL
  • AM Cortisol: 10-18 mcg/dL
  • Pregnenolone: 100-250 ng/dL
  • Estradiol: 50– 250 pg/ mL (women, age dependent)
  • Progesterone: 1-20 ng/mL (women, age dependent)
  • Testosterone: 500-1,000 ng/dL (men) 25-70 ng/dL (women)
• A decrease in serum Vitamin D levels. Normal Vitamin D levels should be 50-80 ng/mL
• An increase in homocysteine levels can occur. Normal homocysteine levels should be less than or equal to 7 μmol/ L (homocysteine is also seen to increase in Type 1)
• Insulin resistance can occur OR insulin levels may be too low

This sub-type responds well to ReCODE but can take a little longer due to the number of contributing factors.

Type 3: Toxic - 'vile' type

This sub-type is more complexed to treat and is characterised by an APOE3 carrier status with poor detoxification ability which includes determining your genotype for key detox genes such as CYPs, GSTM1, GSTTP, and MTHFR. This together with exposure to toxins, especially heavy metals such as mercury, zinc, and copper as well as mold and biotoxins such as tick bites.

This type can often present itself quite early, around the 40s and 50s. 

• Low triglyceride levels as compared to cholesterol levels.
• MRI scans show shrinkage of the hippocampus.
• Neuroinflammation and vascular leaks, which are presented on a specific MRI called FLAIR (Fluid-attenuated inversion recovery) as white spots.
• Decreased zinc levels. Normal levels are between 90-110 mcg/dL.
• Elevated copper levels. Normal copper levels are between 90-110 mcg/dL.
• High blood levels of toxic chemicals such as mercury or mycotoxins (caused by molds).
• The pituitary gland and adrenal glands become dysfunctional, which can show up in lab tests as hormonal abnormalities.

Ordering tests like the HEAVY METAL PROFILE,  TOXIC NON-METAL CHEMICAL PROFILE or the MycoTOX PROFILE are awesome tools for you to measure what toxicity your body has been exposed to. 

Type 4 : Vascular

Type 4 or Vascular AD, is caused by a reduction of blood flow to the brain, which ultimately deprives the brain of essential oxygen and nutrients. The brain is an extremely vascularized tissue, meaning it requires large amounts of oxygen. A lack of oxygen to the brain leads to hypoperfusion (low blood flow) and compromises the blood-brain barrier which allows for harmful substances to leak in and damage neurons. Cerebral vasculature is extremely important as it is one way the body clears the accumulation of amyloid-beta.

It is important to consider the ACE, NOS3, VEGF & AGT genotypes when putting together a prevention plan for this sub-type. 

Characteristics & Biochemical Markers of Type 4

• “Leakiness” present in vascular tissues.
• Individuals with cardiovascular disease have high risk for Type 4 Alzheimer’s.
• These individuals do best when they prioritize healing underlying insulin resistance.

Type 5: Traumatic 

Type 5 or trauma induced Alzheimer’s, results from traumatic brain injuries (TBI) which disrupt normal brain function, including learning and thinking skills. Certain types of TBI’s may increase the risk of developing Alzheimer’s disease years after the injury takes place. One of the most impactful studies showed that those with a history of moderate TBI had a 2.3 times greater risk of developing Alzheimer’s than older adults with no history of a head injury and those with a history of severe TBI had a 4.5 times greater risk. Additional research is needed however to fully understand the relationship between TBI’s and Alzheimer’s disease.

This best DNA test available to determine which sub-type you could be predisposed to, is the GENE-WELL + GENE-DIET test. 

From the above, you should be able to see which path of cognitive decline would apply to you. Armed with this info, you could start with the ReCODE protocol to prevent or reverse signs of cognitive decline.  

Dr. Bredesen recommends that all people over 40 should be empowered with this information. We believe that by doing the recommended genomic testing and biochemistry testing early, you can optimize your health to ensure that you bulletproof yourself against Alzheimer's disease. Keeping in mind that you don't just wake up with Alzheimer's disease but rather you slowly slide from subjective cognitive decline (so-called "brain fog") to mild cognitive impairment towards dementia and Alzheimer's disease. The sooner you can heal the body and optimise the health factors that protect against declining cognition, the greater the opportunity you have to prevent. 

You live in an amazing time where you can determine your specific risk and take action to prevent and support. You can live in the know.