The Illhehad and the Odyssey: Remarkable Progress from Biomarker Testing

By Dale Bredesen, M.D., Chief Science Officer for Apollo Health

The new blood biomarkers are allowing us to look inside the brain — without a spinal tap or PET scan or MRI — for the first time, and the early results coming back are both fascinating and instructive. These results will help to guide us all to improved outcomes, and help us to make the dementia of Alzheimer’s a very rare condition, just as it should be.

We have already seen examples of something quite surprising and exciting: people who are ApoE 4/4 and on the ReCODE Protocol for several years, doing well, and turning out to have normal p-tau 217! This tells us that what we have seen repeatedly in cognitive testing — improvement with an optimized protocol — is reflected in brain chemistry and brain signaling, with a return to normal p-tau 217. This is despite the recent publication showing that, without such intervention, 88% of people with ApoE 4/4 developed cognitive decline.

Following p-tau 217 levels also provides an excellent method to track progress, and determine whether one is on the right path, or whether something additional needs to be addressed. It is complementary to following cognitive status, and provides an objective biochemical measure of status and progress. Furthermore, if p-tau 217 is high, then the other markers — NfL and GFAP — give us an idea of how active the process is: for those with normal NfL and GFAP despite high p-tau 217, the process is relatively inactive and the progress is likely to be slow, whereas for those with high p-tau 217, high NfL (indicating neuronal damage), and high GFAP (indicating inflammation and repair), the process is very active and may well progress rapidly unless treatment is undertaken and optimized.

Another major advantage is that those with cognitive decline unrelated to Alzheimer’s can be identified quickly and treated appropriately — although Alzheimer’s causes the majority of cases of dementia (approximately 60%), there are other conditions that can masquerade as Alzheimer’s, such as Lewy body dementia, vascular dementia, FTD (frontotemporal dementia), and LATE (limbic-predominant age-associated TDP-43 encephalopathy), among others. The good news is that these are fairly easy to distinguish once we know that the Alzheimer’s biomarkers are negative, and these can all be treated (although we have insufficient data on FTD, so it is not yet clear how effectively this can be treated).

We have already made an interesting discovery in follow-up p-tau 217 levels: for those with rapid and significant weight loss (20 pounds or more), the p-tau 217 levels often increase transiently, so it’s a good idea to recheck after a year, when weight has been stable. This effect is exacerbated in those with marked cognitive improvement — which may sound paradoxical (typically we see p-tau 217 coming back to normal as people improve), but during development the p-tau is high as a reflection of active neuroplasticity, so it is very possible that these examples of marked improvement are undergoing a period of active neuroplasticity, with new synapse formation, and follow-up p-tau levels should show a return toward normal.

Complementing p-tau, the NfL and GFAP levels are very revealing, as well. For those with normal p-tau 217 but high NfL, other causes of neuronal damage, such as trauma or FTD or ALS, should be considered. For those with normal p-tau 217 and NfL but high GFAP, the cause of the brain inflammation and repair should be identified, and it is important for those with isolated high GFAP to undergo MRI imaging, since although uncommon, occasionally a high GFAP can indicate a specific type of brain tumor called an astrocytoma (also treatable).

The synergistic combination of BrainScan, ReCODE labs, and the protocol is allowing us all a much deeper and more complete view of ongoing brain processes, and helping us to take a major step forward, making dementia a rare, and ultimately optional, condition.