The new P-tau 217 test is almost here

[SoccerMom]

8000 people! Wow! I will try to attend next year.

SoccerMom, did you get the ratio measured, or just p-tau217? Either way, the result is fairly low! Lots of time to intervene!

Brian

Labcorp just measures the p-tau 217, not the ratio. I'm already "intervening"--that's why I was hoping to see a zero. I guess I will retest in a couple years to see if it goes up.

[Julie G]

Labcorp just measures the p-tau 217, not the ratio. I'm already "intervening"--that's why I was hoping to see a zero. I guess I will retest in a couple years to see if it goes up.

Kudos, SoccerMom, on a good score. I just wanted to remind everyone that the p-tau 217 from Labcorp, however, isn't particularly sensitive. Only two tests (PrecivityAD and BrainScan) are currently run on the C2N platform, which has the highest degree of sensitivity and validation. This might be a good thing to keep in mind for those who are planning to get tested.

[Hazelwood]

Can anyone tell me the difference between the LabCorp p-tau test and the PrecivityAD2 p-tau test? My doc is willing to place the lab orders, I have requested the Precivity test and he has recommended the LabCorp test. I am 4/2 pre-Alz, and wanting to incorporate p-tau : Ab into my testing protocols. Thanks in advance.

[JulieMorris]

Can anyone tell me the difference between the LabCorp p-tau test and the PrecivityAD2 p-tau test? My doc is willing to place the lab orders, I have requested the Precivity test and he has recommended the LabCorp test. I am 4/2 pre-Alz, and wanting to incorporate p-tau : Ab into my testing protocols. Thanks in advance.

Hi Hazelwood-
Hello! I'm a support team intern, and I'd like to welcome you to this site! You have found a very supportive community here. You have some very specific questions about testing, which I am unable to answer, but I'm sure someone will chime in shortly with answers. This is an intelligent, compassionate community and we love to share questions, answers, and stories here. When you feel comfortable, we would love it if you would share a bit more of your own story with us.

You are obviously a very informed, proactive person who advocates for your own health. This is a huge win, and I congratulate you on finding a provider who is willing to order the appropriate testing. Surrounding yourself with support, which may include medical providers, family, friends, and this site is another big advantage to your brain health.

If you haven't already, it would be a great idea to first take a look at our Primer. It is an incredible resource of information about the biochemistry of ApoE4. It offers researched-based prevention strategies and was written by a practicing M.D. with ApoE4. Do not become overwhelmed with all the information. Sometimes it is best to slowly read through it, decide which section resonates with you, and focus on that area first. Remember that small changes can make a big difference to brain health.

The How-To Guide will help you learn how to navigate this site. It includes topics such as navigating the forum, private messaging, and searching.

You can find other members' experiences in Our Stories. Sometimes reading the stories of others helps us realize that we are not alone.

I'm so glad you have joined us on this site. Please feel free to reach out anytime with questions or if you just need support. You are not alone. We are here for you.

Take care,
Julie

[NF52]

Can anyone tell me the difference between the LabCorp p-tau test and the PrecivityAD2 p-tau test? My doc is willing to place the lab orders, I have requested the Precivity test and he has recommended the LabCorp test. I am 4/2 pre-Alz, and wanting to incorporate p-tau : Ab into my testing protocols. Thanks in advance.

Hi Hazlewood,

You may want to ask your doctor why he recommends the LapCorp test (possibly P-tau 181or P-tau 217) over the PrecivityAD2 test. It's possible he's more familiar with what the report looks like. Here's a sample report from the p-tau 217 test on LabCorp's website: https://files.labcorp.com/testmenu-d8/s ... 484390.pdf. This sample report shows a "normal result" with a p-tau score of 0.08, which is below the stated baseline of scores higher than 0.18 that indicates a higher likelihood of amyloid plaques if a PET scan was given.

He may be looking at cost also, since if you are not experiencing memory concerns, it's unlikely your health insurance will cover the cost of either test. I don't know what either test costs but he could probably tell you that. Here is some information on Precivity's options for paying: https://precivityad.com/cost-billing

The PrecivityAD2™ test is a newer version of the original test and uses an algorithm using Aβ42/40 and p-tau217/np-tau217 (%p-tau217) ratios and gives a predictive score, which you can read about here: https://precivityad.com/precivityad2-hcp It has also been used extensively in Sweden in clinical practice along with PET scans to see both if it is accurate in predicting a "positive" amyloid PET scan and if it helps doctors make a more accurate diagnosis of whether someone with memory issues or other symptoms suggestive of Alzheimer's actually has the biomarker of amyloid and/or tau. Here's a recent newsletter about that, which references both the Swedish study and a peer-reviewed article published just a few weeks ago in the Journal of the American Medical Assn: Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care
According to the latest studies of Precivity in clinical use with people with referrals to memory clinics, the test has an 88% sensitivity rate, meaning 88% of those who actually do end up with a "positive" amyloid PET score had a "positive" on the PrecivityAD2 result. It also had an 89% specificity score, meaning only 11% of people who ended up with a positive PET scan were told they were negative. Overall, the "area under the curve" of people diagnosed accurately was about 94%, which is equivalent to the results of a lumbar puncture test compared to a PET scan.

I've personally used Lab Corp for lots of tests over the years for things like B12, glucose, cholesterol, etc. But if I were to get an amyloid prediction test, I would go with PrecivityAD2™ based on what I've read and heard.

Nancy

[Brian4]

I just wanted to remind everyone that the p-tau 217 from Labcorp, however, isn't particularly sensitive. Only two tests (PrecivityAD and BrainScan) are currently run on the C2N platform, which has the highest degree of sensitivity and validation. This might be a good thing to keep in mind for those who are planning to get tested.

Hey Julie! Since some of us can get the LabCorp test cheaply, I'd love to know why you think the LabCorp test isn't particularly sensitive.

Here's what I read on the BrainScan website:

"Unlike standard p-tau 217 tests, which do not turn positive until significant symptoms have occurred, high-sensitivity p-tau 217 by Neurocode is more sensitive."

There's a link to this article (which I missed in my previous post; apologies!), for more information about the p-tau217 test:

https://jamanetwork.com/journals/jamane ... le/2813751

There, I read:

"Novel p-Tau217 Assay
The commercial ALZpath pTau217 assay for p-tau217 uses a proprietary monoclonal p-tau217 specific capture antibody, an N-terminal detector antibody, and a peptide calibrator. It has been validated as a fit-for-purpose assay with a limit of detection of 0.0052 to 0.0074 pg/mL, a functional lower limit of quantification of 0.06 pg/mL, and a dynamic range of 0.007 to 30 pg/mL."

https://www.labcorp.com/tests/484390/ph ... 217-plasma

At the LabCorp site, I read:

"This test is performed by Fujirebio Lumipulse chemiluminescent enzyme immunoassay (CLEIA). Values obtained with different methods cannot be used interchangeably. The validated limit of quantification is 0.06 pg/mL. Assay detection limit is 0.03 pg/mL."

"Functional lower limit" I'm interpreting as validated lower limit. So that would mean the two tests are just as sensitive at low levels of p-tau 217, since the non-functional/-validated detection limit wouldn't be relevant.

What am I missing?

Thanks!
Brian

[Julie G]

Hey Julie! Since some of us can get the LabCorp test cheaply, I'd love to know why you think the LabCorp test isn't particularly sensitive.

Here's what I read on the BrainScan website:

"Unlike standard p-tau 217 tests, which do not turn positive until significant symptoms have occurred, high-sensitivity p-tau 217 by Neurocode is more sensitive."

There's a link to this article (which I missed in my previous post; apologies!), for more information about the p-tau217 test:

https://jamanetwork.com/journals/jamane ... le/2813751

There, I read:

"Novel p-Tau217 Assay
The commercial ALZpath pTau217 assay for p-tau217 uses a proprietary monoclonal p-tau217 specific capture antibody, an N-terminal detector antibody, and a peptide calibrator. It has been validated as a fit-for-purpose assay with a limit of detection of 0.0052 to 0.0074 pg/mL, a functional lower limit of quantification of 0.06 pg/mL, and a dynamic range of 0.007 to 30 pg/mL."

https://www.labcorp.com/tests/484390/ph ... 217-plasma

At the LabCorp site, I read:

"This test is performed by Fujirebio Lumipulse chemiluminescent enzyme immunoassay (CLEIA). Values obtained with different methods cannot be used interchangeably. The validated limit of quantification is 0.06 pg/mL. Assay detection limit is 0.03 pg/mL."

"Functional lower limit" I'm interpreting as validated lower limit. So that would mean the two tests are just as sensitive at low levels of p-tau 217, since the non-functional/-validated detection limit wouldn't be relevant.

What am I missing?

Thanks!
Brian

Great question. I reached out to the folks at Neurocode, who run the BrainScan testing and posed your question. See their response below:

The confusion here is a conflation of different uses of the term sensitivity: clinical vs analytical.

You’ve referenced the limits of quantification, which is a description of how small a quantity of the analyte can be detected (the analytical "sensitivity"). Most samples run > 0.1 ng/L, so it doesn’t have much of an effect for either assay.

Whereas BrainScan is referencing the clinical sensitivity: how accurately the test can discriminate amyloid-positive samples from amyloid-negative samples (as determined by PET or postmortem pathology). This is a measure of how sensitive the test is in detecting amyloid pathology.

BrainScan has observed this to be higher compared to the Labcorp assay. BrainScan is 93-95% and Labcorp is ~80-90%. This can be found in the pre-print (table 4 compared to table 5): Alzheimer’s disease clinical decision points for two plasma p-tau217 laboratory developed tests in neuropathology confirmed samples | medRxiv.

The real issue with Labcorp and Quest is they are using a single cut-off, and additional follow-up will be required (PET or CSF to confirm the results). A single cut-off is not recommended for this test because it doesn’t offer clear negative or positive results.

This paper provides a nice overview of sensitivity, specificity, and accuracy for your reference: Diagnostic Testing Accuracy: Sensitivity, Specificity, Predictive Values and Likelihood Ratios - StatPearls - NCBI Bookshelf (nih.gov)

[houstonguy]

New Tau 217 test vs Pet Scan?

If I can get Medicare to pay for the Pet Scan which test should I get?

Jerry, 74 yr old APOE 4/4 doing basically ok, but some recall problems. Some days better than others. I Was in the Pointer Study (Finger Replication Study) with repeated cognitive testing last time about 4 months ago and not recommended for treatment.

[NF52]

New Tau 217 test vs Pet Scan?

If I can get Medicare to pay for the Pet Scan which test should I get?

Jerry, 74 yr old APOE 4/4 doing basically ok, but some recall problems. Some days better than others. I Was in the Pointer Study (Finger Replication Study) with repeated cognitive testing last time about 4 months ago and not recommended for treatment.

Hi Jerry!

The short answer is, as usual, "It depends." Two factors may be important for your decision.

The first is whether your regional Medicare program allows for coverage of a PET scan by your primary doctor or a specialist, not the Pointer Study doctor, as part of a workup to determine if you have Mild Cognitive Impairment. Right now Medicare does not cover PET scans automatically for people like you and me with ApoE 4/4, if we have normal cognition, even though we are likely to have a positive scan. (I had my first at age 65 in a clinical trial and have had more since as part of the AHEAD study).

The Centers for Medicare Services (CMS) approved the use of amyloid PET scans, CSF tests (lumbar punctures) and amyloid blood tests as of October 2023, but they didn't mandate it across the country. If you have a Medicare Advantage plan along with basic Medicare, the Advantage plan may not cover the PET scan. You should be able to contact your plan about coverage and any co-pays that you would be responsible for paying.

Rather than issue a National Coverage Determination that would mandate amyloid PET coverage, however, CMS left the issue up to the 12 Medicare Administrative Contractors to decide for their respective regions... In addition, Medicare Advantage plans, which cover a third of seniors, may choose to reimburse differently than does traditional Medicare.

AlzForum: After a Decade, Amyloid PET Scans Receive Broad Insurance Coverage.

The second factor is two-fold: how much detail do you want to know, and how much of the time and inconvenience of a PET scan are you willing to spend for that ?

The blood tests are about 90-95% accurate compared to a PET scan for someone who has an actual diagnosis of Alzheimer's dementia. If the blood tests is "positive", the PET scan almost always will be also for people with Alzheimer's dementia.. About 30% of people with a diagnosis actually come back with a negative on both, because their cognitive and other issues are caused by vascular dementia, Lewy body disease, TDP-43 disease, (called LATE as an acronym) or other factors like inflammation or prior head injury.

For people like me, who have normal cognition and also had elevated levels of amyloid plaques (before a clinical trial) a "positive" test is about 85% likely to be correctly predicting a positive PET scan. A "negative" test is almost 100% likely to predict a negative PET scan. About 10-15% of people with memory complaints but not a diagnosis are likely to get an "intermediate" result from the blood test. That would need to be followed up with a PET scan to confirm whether or not the person has a significant amount of plaque.

It might seem like the easy thing to do is to just get the PET scan, but those are far costlier than MRIs and take longer to schedule, often a month or more. The material used has to be refrigerated and shipped carefully from distributors and then it has to be used within a specific amount of time. (My AHEAD site gets their PET scan material delivered by a truck that travels 5 hours.) You need to arrive at the PET scan site about an hour before your scheduled scan, get hooked up to an IV, with the "solution" infused, and the IV then removed. Then you sit quietly for about 50 minutes before you're brought into the scanning room, with about 30 minutes in the PET scanner. It's much quieter than an MRI, but if you're claustrophobic, it might not be your favorite place. So the whole process takes about 90 minutes, plus travel time.

Results are returned to your doctor within about a week with a "centiloid" value of any amyloid you have. Less than 20 centiloids is considered "not positive" by most researchers; 20-39 is considered "intermediate" level and 40 and above is considered "elevated". For what it's worth, I had an elevated level at age 65 with ApoE 4/4, as did "ChicagoGirl" who posts about being in the AHEAD study. People with an Alzheimer's diagnosis may have levels up to 100 centiloids or more, although they tend to drop later in the disease.

You may want to think about what you will do with this knowledge, since having the biomarker of Alzheimer's disease is not the same having MCI or Alzheimer's mild dementia. There are likely new trials of both anti-amyloid and anti-tau drugs, including ALZ-801 that shows promise in ApoE 4/4 carriers, coming soon. If you want to be ready for those, one of these tests could help. If not, maybe life is fine without knowing your amyloid status.

Kudos to you for participating in the US Pointer Study--it's proving that multiple components of lifestyle interventions make a real difference in health.

Finally, when you say that you were not recommended for treatment, I assume the Pointer Study site doctor told you that you would not be eligible for either lecanemab (Leqembi) or donanemab (Kisluna) because your cognitive scores are NOT in the Mild Cognitive Impairment (MCI) range.

If they told you that you wouldn't be eligible for the treatment because you have ApoE 4/4, but that you are scoring in the MCI range, any decision to exclude or not recommend ApoE 4/4 carriers for an anti-amyloid drug should be done with a careful screening and discussion with the neurologist who refers you, usually at a memory center or an academic center prescribing those drugs. In some areas of the country, wait times are up to nine months, due to high demand and not enough neurologists.

Keep us posted, if you're comfortable sharing what you decide.

Nancy

[houstonguy]

Thanks, Nancy. About a week ago a friend told me he had Medicare pay for the Pet Scan in Houston with Medicare. Don't know if he has straight Medicare or a Advantage Plan like I do. He was very worried due to family history and his perceived problems. It came back negative. He is very grateful. I guess I should find out.

As far as what I would do about with the knowledge if it came back positive it would make me more strict in lifestyle since I have slacked off a bit, though am still about 90% Bredesen Protocol, which is stricter than Pointer.

What is the AHEAD study? They tried to recruit me to a drug study after Pointer. After all the news about the massaging of the data on the seminal amyloid study and my study of the Bredesen Protocol I may be too negative about the drugs. I guess I should renew my study of Alzheimers on APOE4.info which I have also slacked off on.