Let's start with APOE The APOEε4 gene allele is the biggest genetic risk factor for Alzheimer’s disease APOEε4/ε4 is considered the highest risk, ε2/ε3 the lowest, and ε3/ε3 intermediate risk

People with the APOEε2/ε2 genotype have been seen to have a 66% lower odds ratio of Alzheimer’s compared to those with the APOEε2/ε3 genotype, 87% lower than those with APOEε3/ε3, and 99.6% lower than those with APOEε4/ε4 PMID: 32015339

APOEε2 is also linked to longevity independent of Alzheimer's (PMID: 33074098) Having the ε2/ε2 or ε2/ε3 genotype is linked to a greater odds of reaching extreme longevity and reduced risk of mortality compared to ε3/ε3 (PMID: 30060062)

APOE is genetically determined so you need to get a DNA test Your genes don't change so this is a once in a lifetime test

Moving on with Lp(a) Lp(a) or lipoprotein(a) is the strongest genetically determined atherogenic lipoprotein with 90% of Lp(a) levels being explained by a single gene called LPA Lp(a) levels can vary 1000-fold between people, ranging from close to 0 to 300 mg/dL

Lp(a) below 50 mg/dL is considered normal, but above 5 already is linked to higher risk of heart disease (PMID: 20965889) A 2021 large UK Biobank study among 460,000 subjects discovered a linear increase in ASCVD risk after an Lp(a) concentration of 8 mg/dL (PMID: 33115266)

Lp(a) is like 90% genetically determined and you can't affect it significantly with diet or lifestyle But getting a blood test for it at least once can reveal where's your genetic setpoint if you will, which then helps you to optimize the other risk factors

Get my free annual bloodwork cheat sheet for what other markers are worth testing: https://www.siimland.co/bloodw...

@siimland A single test could reveal your genetic predisposition for Alzheimer's or heart disease. The APOE gene is a powerful predictor of Alzheimer's risk, while Lp(a) levels strongly influence cardiovascular outcomes. Knowing our status can empower targeted prevention efforts.

@siimland Explain how a genetically derived lipoprotein can be atherogenic? I thought genes were about survival of the fittest and if so what ADVANTAGES did apoE4 and lpa give to our ancestors that allowed them to procreate so we could be here?

@siimland Why test is genetic predisposition is not actionable.

@siimland Then what?

@siimland Interesting points, Siim. Genetic testing can indeed provide insights into personal health risks. However, I am curious about how you suggest people use this information. Should they consult with a healthcare professional to interpret results, or do you recommend specific

@siimland Testing for rs1803274 (BCHE) is probably equally as valuable. Its associated with a high sensitivity to pesticides, and of pesticides strongly increasing alzheimer's risk. Relevant only bc most people's exposure is probably daily with every meal. Small choice, big impact.

@siimland I am dealing with the sequelae of finding the high Lp(a), but it had a purpose in how hard to go after LDL and then jump on obicetrapib or pelacarsen when available. For APOE, not sure I want to know yet if it won’t change my management yet.

@siimland I ask my aunts and mom if they ever saw someone with Alzheimer’s or dementia when they were kids or adults and they never did. They started seeing that around the 90’s. Weird

@siimland What marker is this on 23 and me when you have your raw data?

@siimland Stop saying Risk factor. https://pmc.ncbi.nlm.nih.gov/a...

@siimland @grok How can I test for this?

@siimland Why? What are you going to do about it?

@siimland As a primary care physician, I order Lp(a) on everyone but never order Apoe. Why? Because there is no treatment for Alzheimer's. Why deal with that emotional burden? A patient of mine had her teenage daughter tested and she was positive, now has tremendous remorse.