P-tau217 Testing

There is a lot of excitement over the possibility that p-tau 217 testing could “transform AD testing.” For example, see this summary from the Alzheimer’s Association.

It is my opinion that p-tau 217 is not quite ready to be used as the single test of whether someone with MCI or clinically determined mild AD should be given anti-amyloid therapy. There are several reasons for this viewpoint, including the following:

• Many of the studies supporting p-tau 217 included small numbers of cognitively normal participants with advanced age, participants with MCI of all varieties, and participants with other forms of mild dementia that may be mistaken for MCI due to AD and that are unlikely to respond to anti-amyloid therapy.
• Test characteristics such as sensitivity and specificity depend on prevalence in the population, and are likely to change drastically as more cognitively normal elderly with MCI due to other conditions (including normal aging) present to the DNAC for further testing.
• Tau is thought to be “downstream” to the amyloid accumulation that is a hallmark of AD neuropathology and is thus (in theory) a later indicator of pathology.
• Many disorders can cause tauopathy besides AD.

Also, the decision to proceed to p-tau 217 testing depends on whether other inclusion/exclusion criteria are fulfilled:

• Cognitive and behavioral profile are consistent with Alzheimer’s or Mild Cognitive Impairment.
• Blood testing excludes treatable causes of dementia, like syphilis, hypothyroidism, thiamine or B12 deficiency, etc.
• MRI scan excludes substantial amyloid related imaging abnormalities (ARIA).
• MRI excludes other causes of dementia like normal pressure hydrocephalus, vascular dementia, brain tumor, etc.
• Weight is not too thin or too heavy for anti-amyloid therapies.
• No problem with uncontrolled seizures.
• No prior history of lobar or basal ganglia or subarachnoid/subdural hemorrhage.

Once you have made the decision to get the p-tau 217 testing, and receive the results, you are ready to move to the next step.

Bearing all these considerations in mind, choose Positive P-tau217 ONLY if the test results are interpreted by the lab as suggestive of AD. Otherwise, choose Negative or Inderminate P-tau217.