As most of you know, I recently went back for my brain health and APOE4-focused assessments at RetainMed in Boca Raton to meet with specially trained Nurse Practitioners utilizing Dr. Richard Isaacson’s precision prevention methodology, and get my results from the labs taken during my first visit on July 1. Here’s the recap. The photo below was taken after my results were explained and I was preparing to head home! I can't say enough about the RetainMed team—a phenomenal and incredibly knowledgeable group of people using cutting-edge testing and the latest science to help us better understand and protect our brain health.
This was my first brain biomarker test in the eight years I’ve known of my increased AD risk as an APOE4/4 carrier. While I’ve been tracking all the usual suspects - lipids, glucose, inflammation, sleep, exercise and other metabolic markers - I felt I’d postponed the brain biomarker tests long enough. When the opportunity to visit RetainMed presented itself, I seized the chance to be tested and have a licensed clinician with subject matter expertise present when the verdict was delivered who could explain the results and any potential actions or interventions I might need. RetainMed’s program was very appealing since it incorporates newer blood-based AD biomarkers along with genetics, metabolic, cardiovascular, inflammatory, and hormonal risk, lifestyle and nutrition factors and individualized follow-up recommendations!
In the following deep dive, I will share what was tested, where my results fell directionally and what I’ve learned from the process.
First, I’ll cut to the chase
The overall outcome was reassuring, with a few barely-above-range markers to follow and keep an eye on! Despite being in my 70s and carrying two copies of APOE4, my amyloid blood markers were favorable for my age and genetic status.
One of the biomarkers I found pretty reassuring was my amyloid-beta 42/40 ratio.
Amyloid-beta exists in several forms, including Aβ40 and Aβ42. Aβ42, being the stickier form of amyloid, has a greater tendency to aggregate in the brain. Rather than looking simply at how much Aβ42 is circulating, researchers have found that the ratio of Aβ42 to Aβ40 provides considerably more useful information.
A lower Aβ42/40 ratio in the blood is associated with greater cerebral amyloid deposition, while a higher ratio is more favorable. Perhaps counterintuitively, a higher Aβ42/40 ratio in the blood is considered more favorable. As RetainMed explained it to me, one way to think about this is that my brain and body are working together to efficiently dispose of these proteins. Lifestyle behaviors such as exercise may help support this process, while adequate sleep and other factors support the brain's “trash disposal” and clearance systems.
My ratio fell comfortably within RetainMed’s normal age-adjusted range and, interestingly, at 0.07348 fell within the desirable range for those 25 years younger (which is >0.0713)! That was quite reassuring. One of the more helpful components of the lab reports is that the normal (or expected values) for blood testing results was broken down into ranges based on a person’s age and biological sex, allowing for more of a customized comparison.
It does not prove that I have zero toxic amyloid build-up in my brain. A blood biomarker isn’t the same thing as an amyloid PET scan. It’s also important to note that beta amyloid does occur naturally in the brain as a product of regular brain cell metabolism and is present in healthy brains throughout life. But the risk of cognitive decline related to Alzheimer’s disease pathology occurs when that beta amyloid aggregates improperly and clearance is impaired.
But, now being a few days away from my 74th birthday, I will definitely put a favorable amyloid ratio in the GOOD NEWS column.
Tau was more nuanced
RetainMed also measured two phosphorylated tau markers: p-tau181 and p-tau217.
These proteins have become increasingly important Alzheimer’s biomarkers.
Tau normally helps stabilize the internal structure of neurons. In Alzheimer’s disease, abnormal phosphorylation and aggregation of tau become part of the disease process.
Both of my individual p-tau measurements remained within the laboratory’s normal ranges.
My p-tau181 was normal and reassuring.
My p-tau217 was also normal, which is very reassuring, but through a careful precision-prevention lens, it’s still a number they want me to keep an eye on over time. For me, it’s another reminder to stay proactive about the things I can control—supporting my brain health, addressing my individual risk factors, and doing what I can to help keep tau from trending in the wrong direction as I age. That’s where I’m personally hedging my bets on access to Obicetrapib as soon as it’s available in Europe (although the RetainMed team isn’t quite sure I even need that just yet). While normal, even a modest reduction in p-tau217 would move me more comfortably into the optimal range.
It’s important, however, not to directly compare the cutoff on my report with Mayo Clinic’s p-tau217 cutoff as though they are interchangeable-because they are not. Different assays use different reference ranges and thresholds. Mayo’s current plasma p-tau217 interpretation considers ≤0.185 pg/mL negative, 0.186–0.324 pg/mL intermediate, and ≥0.325 pg/mL positive. A positive result is consistent with the presence of Alzheimer-associated neuropathological changes. As an APOE4 carrier, I don’t want to get close to that territory!
A marker can still fall within a population reference range while its trajectory over time may eventually tell us something equally (or even more) important.
For me, p-tau217 has therefore become a marker I want to watch — not a marker I am panicking about.
The ratios added another layer
RetainMed also calculated ratios comparing phosphorylated tau with Aβ42.
My p-tau181/Aβ42 ratio was considered optimal.
My p-tau217/Aβ42 ratio was mildly elevated according to their reference system.
Importantly, this did not appear to be driven by a poor Aβ42/40 ratio. My amyloid ratio itself was favorable.
GFAP was the result that initially got my attention
Another marker they measured was GFAP - glial fibrillary acidic protein.
GFAP is produced primarily by astrocytes, the incredibly important support cells that surround and interact with neurons.
When astrocytes become activated or stressed, GFAP in the blood can increase. Researchers are studying it as a marker of neuroinflammation and neurodegenerative processes.
Mine was considered mildly elevated according to RetainMed’s reference ranges.
I subsequently did some digging of my own and discovered that GFAP interpretation is not nearly as simple as a single universal cutoff. Levels rise substantially with age, different assays produce different values, and age-adjusted reference intervals matter.
So I am much less alarmed by this result than I initially was.
RetainMed also emphasized that GFAP is not specific for Alzheimer’s disease. It can be influenced by numerous biological and medical factors (including metabolic health, inflammatory conditions, infections, amongst quite a few others.).
Something worth watching to more globally understand how brains age, but not clear evidence of one specific neurodegenerative disease.
And that brings me to another biomarker that I found particularly reassuring.
My NfL was normal
Neurofilament light chain, or NfL, is a structural protein found in neuronal axons.
When neurons or their axons are injured, NfL can escape into cerebrospinal fluid and eventually into blood.
Elevated NfL can occur in numerous neurological conditions, so it isn’t an Alzheimer’s-specific marker. But it is useful as a marker of neuroaxonal injury.
Mine was comfortably within the normal range - and fell within the expected range for ages 40-49.
In other words, the panel showed no elevated NfL signal suggesting active neuroaxonal injury.
My genetics offered another encouraging finding
In addition to confirming gene variants I was already aware of — APOE4/4 and MTHFR C677T homozygosity — the testing also confirmed my protective KLOTHO genotype. While I believed to have the Klotho variant based on my 23andme results, I wasn’t 100% certain.
I carry one copy of a KLOTHO variant that has been associated in some research with healthy aging, cognitive resilience and longevity.
The science around KLOTHO is still evolving, and it absolutely does not erase APOE4 risk.
But I found it encouraging for another reason:
APOE is not the entire genome.
We tend to talk about APOE4 as though one gene determines our neurological destiny. In fact, thousands of genetic variants, environmental exposures, metabolic factors and lifestyle choices interact over decades.
That is why two people with exactly the same APOE genotype can age very differently.
Along these lines, I also learned about my results on their new APOE4 protein expression test, and a related APOE blood test that measures overall APOE gene function in real-time. As I’ve written about previously, genes are only one part of a person’s risk equation and don’t change over time, but the amount of protein made (or expressed) by a gene can fluctuate. Using a car analogy, the APOE4 genetic variant is like a car engine (that you can’t readily change) but a protein test like this is like an engine light that may go on or off depending on how the car is running. Put in high quality fuel (e.g., nutrition) and perform routine maintenance (e.g., medical care), and the car runs in peak performance. Yet if lifestyle and other medical risk factors are not optimized, it is theorized that more APOE4 protein would be produced, fast-forwarding amyloid accumulation, and the engine warning light may turn “on” - signaling a potential problem in the future. While research in this area is still in its early stages, measuring a baseline that we can monitor over time may be an important emerging tool to help people with one or more copies of the APOE4 genetic variant.
Cardiovascular health looked very good
The cardiovascular portion of my evaluation was also reassuring.
My atherogenic cholesterol markers were extremely well controlled, including LDL-related measures and ApoB. RetainMed’s ApoB target for APOE4 carriers similar to me is <55 mg/dL.
Their emphasis on lipid markers is obvious, and from what I’ve heard Dr. Isaacson say more than once, those carrying APOE4 had better have their lipids in a good place. With so much misinformation online — such as people taking fellow APOE4/4 carrier Nick Norwitz’s self-experimentation with high cholesterol in LMHR phenotypes and extrapolating from it that it’s perfectly OK for APOE4 carriers to ignore high LDL/ApoB as long as their inflammation is low and their CAC score is ZERO — it’s eyebrow-raising, to say the least. I’ve personally heard Nick Norwitz say more than once that the long-term effects of high cholesterol in LMHR phenotypes are not known.
I firmly believe Alzheimer’s prevention and cardiovascular prevention should not be viewed as separate projects. And while the internet continues to perpetuate claims about statin evils and cholesterol benefits, the nuance of individual risk factors and biology is often entirely missed.
For APOE4 carriers in particular, I continue to believe that maintaining excellent vascular health is one of the most important modifiable pieces of the prevention puzzle. And the science appears to be pretty clear that reducing atherogenic lipid burden is beneficial for cardiovascular risk, which is itself relevant to brain health. Obicetrapib’s BROADWAY trial and the resulting exploratory p-tau217 findings in APOE4/4 carriers add an intriguing piece to that discussion.
My fatty acids were another bright spot
The Boston Heart testing included a fairly sophisticated fatty-acid panel.
My omega-3 status and DHA were considered very well optimized.
That was gratifying because DHA is a major structural fatty acid in neuronal membranes, and maintaining good omega-3 status has been a deliberate part of my nutritional strategy for years.
So what happens next?
This was probably the most important part of my follow-up visit.
RetainMed was very clear that these blood biomarkers are not intended to diagnose Alzheimer’s disease. And that the preventive brain health journey is a marathon - not a sprint.
Their recommendation was to establish care with a neurologist — particularly in light of my advancing age — and create a proper neurological baseline.
That may include:
● comprehensive neuropsychological testing
● a baseline structural brain MRI, preferably with volumetric analysis
● additional testing the neurologist considers appropriate
Once that baseline is established, the plan is to repeat selected blood biomarkers periodically and look at trajectory.
This is where prevention medicine is headed
What excites me most about this experience isn’t my individual result – although I was very pleased with it. It is the possibility that we are moving toward a very different model of Alzheimer’s prevention.
In the past, waiting for memory loss, poor cognitive test results or — God forbid — an AD diagnosis was the norm.
Today, we have far better tools for identifying risk and biological changes earlier, along with interventions that may modify risk factors and, in some cases, disease biomarkers. Whether those changes translate into prevention or reversal of Alzheimer’s disease depends on the intervention and the individual, so I don’t think we can yet say broadly that interventions can “halt decline” or “reverse damage.”
But we are indeed living in exciting times!
In Conclusion
Following my test-results review, I received a detailed copy of everything, along with explanations and numerous educational materials and reference links to learn more. It also included recommendations for additional optional testing, medication adjustments, supplements I should continue, those that are optional, and those that aren’t really needed — all of which I can use for guidance in my ongoing effort to maintain my cognitive function and enjoy my life until that last breath! I am very grateful to the RetainMed team, and to Dr. Isaacson for his guidance and for training the team in his precision-prevention approach. Most of all, I’m grateful for the reassurance this experience has given me.
I plan on returning to RetainMed in the future to track my markers and stay on top of my brain health. Having a competent partner to do that with has been life-changing.
I’m writing an article on Klotho right now and I’m friends with Dena Dubal (did a lot of the foundational Klotho work). If you’ve got that variant , you’re very very lucky! It is a very potent mitigator of a whole host of negative genetics, especially apoe4! 🎉
Exciting times!