Summary
What are p-Tau217 and p-Tau181 tests?
p-Tau217 and p-Tau181 are blood tests that measure abnormal forms of tau protein associated with Alzheimer’s disease.
Tau is normally found inside brain nerve cells, where it helps support their structure. In Alzheimer’s disease, tau becomes abnormal and forms tangles that interfere with the normal function of brain cells.
p-Tau testing is intended for people aged 50 years and older who have problems with memory or thinking and are being assessed for Alzheimer’s disease or other causes of cognitive decline.
They are not intended to screen people without symptoms or predict whether they will develop Alzheimer’s disease in the future.
Measuring p-Tau in blood provides a low invasive way to identify people who are likely to have Alzheimer’s-related changes in the brain and who may need further specialist assessment.
Research shows that p-Tau217 and p-Tau181 can detect Alzheimer’s-related changes, sometimes before memory problems develop. However, the strongest evidence for their clinical use is in older people who already have memory or thinking problems. Alzheimer’s-related brain changes become more common with age, so an abnormal p-Tau result in an older person is more likely to represent Alzheimer’s disease than the same result in a younger person.
What is tau protein?
Tau is a normal protein found inside brain nerve cells (neurons). Its main role is to support and stabilise structures called microtubules, which act like tracks that transport nutrients and other materials around the cell. By attaching to microtubules, tau helps keep them stable so materials can move efficiently through the neuron.
Tau normally undergoes chemical changes, including the addition of phosphate groups - these are small chemical tags that cells add to proteins to change how they behave. This process, called phosphorylation, is one of the ways cells control biological activities. Because phosphate groups carry a strong negative electrical charge, adding or removing them can allow cells to adjust their activities as needed.
A small amount of phosphorylation is normal, but if too many phosphate groups are attached, tau is said to be hyperphosphorylated. It loses its ability to bind properly to microtubules, causing the microtubules to become unstable and begin to break down.
The abnormal tau proteins stick together, forming small clumps. These clumps join to form twisted fibres, which build up inside neurons and become neurofibrillary tangles, sometimes called tau neurofibrillary tangles.
This is a problem because the neuron's transport system becomes disrupted and communication between brain nerve cells is impaired. As more cells are affected, problems with memory and thinking develops.
What causes tau to become abnormal?
Normally, phosphorylation acts like a light switch that can be turned on and off as needed. In hyperphosphorylation, this balance is disrupted because enzymes that add phosphates (kinases) become more active, or enzymes that remove them (phosphatases) become less active.
The exact cause of tau hyperphosphorylation is not fully understood, but it is strongly associated with the build-up of amyloid plaque, which are normally automatically cleared from the brain. A build-up of amyloid plaque has long been recognised as a feature of Alzheimer’s disease.
Amyloid plaque and abnormal tau in Alzheimer’s disease
In Alzheimer’s disease, two abnormal proteins build up in the brain - amyloid plaque between brain nerve cells and tau tangles inside brain nerve cells. Abnormal tau levels correlate with amyloid pathology and neurodegeneration.
How measuring abnormal tau can help identify Alzheimer’s disease
Hyperphosphorylated tau can leak out of brain nerve cells and enter the cerebrospinal fluid (CSF) – the clear fluid around the brain and spine - and from there go into the bloodstream.
Measuring abnormal tau levels in blood or CSF can help assess the likelihood of Alzheimer's disease.
In the past, measuring abnormal tau in the blood has been difficult mainly because only very small amounts reach the bloodstream and tau can be phosphorylated in many different places.
Older laboratory methods were not sensitive enough to detect tau reliably but now we have newer highly sensitive laboratory assays.
What are p-Tau217 and p-Tau181?
Tau is a protein. Proteins are the body’s building blocks, and each protein is built from a chain of smaller units called amino acids arranged in a specific order.
p-Tau is an abnormal form of tau. The ‘p’ stands for phosphorylation. p-Tau217 refers to a phosphate group attached at amino acid position 217 and p-Tau181 refers to a phosphate group attached at amino acid position 181 of the tau protein.
p-Tau 217 has been shown to be able to identify, with a high degree of accuracy, people with amyloid pathology. An elevated p-Tau217 blood test result is consistent with an abnormal amyloid-positron emission tomography (PET) scan result. This result is consistent with the presence of pathological changes associated with Alzheimer’s disease.
p-Tau181 is termed a ‘rule-out’ test. This means that a normal result can help exclude Alzheimer's disease, but a higher level of p-Tau181 does not necessarily mean a person has the condition. Increased p-Tau181 levels also occur in other neurological conditions that cause brain cell injury or inflammation, such as stroke or traumatic brain injury. A normal result makes Alzheimer's disease less likely, while a raised result may indicate the need for further testing.
Having the test
Sample
Blood
Any preparation?
None
Your results
Results reporting is not yet fully standardised across all Australian laboratories, but a report typically looks similar to other pathology reports, with a result, a cut-off level (rather than a reference interval), an interpretation and the laboratory’s comments.
Many blood tests results are compared to reference intervals (sometimes called a normal range). Reference intervals are the range of results expected in healthy people. When compared against them results may be flagged high or low if they sit outside this range.
What are cut-offs?
Reference intervals for p-Tau tests are more complicated. With p-Tau tests laboratories use clinical decision limits (cut-offs) rather than conventional reference intervals. These cut-offs are considered to best distinguish people with amyloid-related Alzheimer's disease from those without it.
P-tau levels in the blood tend to increase gradually as Alzheimer's disease develops, so there is no single level that perfectly separates affected and unaffected people.
Test results and cut-offs can vary between laboratories and testing platforms. A result from one laboratory may not be directly comparable to another laboratory that uses a different assay.
| A typical report for p-Tau181 and p-Tau217 may therefore include wording such as: | |
| Result | Possible meaning |
| Below cut-off (negative) | A normal (negative) result is consistent with a negative (normal) amyloid-PET scan result. This result indicates a reduced likelihood that the person has changes associated with Alzheimer’s disease. With Alzheimer's disease pathology unlikely, your doctor may look for other causes of cognitive impairment (thinking and memory issues). |
| Intermediate range | An intermediate result cannot accurately differentiate between the presence or absence of pathological changes associated with Alzheimer’s disease. Further testing, with PET scanning or cerebrospinal fluid testing is needed to determine the likelihood of pathological changes associated with Alzheimer’s disease. |
| Above cut-off (positive) | Alzheimer's disease pathology likely, confirmatory testing required. |
Terms you might come across
Treatment
Disease-modifying treatments are now available for selected people with early Alzheimer's disease. These treatments aim to slow progression rather than cure the disease.
Examples include:
Before these medicines can be prescribed, Alzheimer's disease usually needs to be confirmed with evidence of amyloid pathology, often using amyloid PET imaging or cerebrospinal fluid biomarkers.
Any more to know?
The APOE gene
The APOE gene provides instructions for making apolipoprotein E, a protein that helps transport cholesterol and other fats around the body. It also has important roles in the brain.
Having an APOE variant called APOE ε4 increases the likelihood of developing Alzheimer’s disease, but it does not mean that you have, or will develop, the disease. Many people carry these variants. Similarly, not having APOE ε4 does not mean you will develop Alzheimer’s disease. For this reason, APOE genetic testing is generally not used for predicting whether a healthy person will develop Alzheimer’s disease.
Treatment with anti-amyloid immunotherapies
There is one important use of APOE testing and this is before treatment with some anti-amyloid drugs. People carrying APOE ε4—particularly those with two copies—have a higher risk of ARIA (amyloid-related imaging abnormalities) during treatment. ARIA can cause swelling or small areas of bleeding in the brain. Knowing your APOE status can help assess this risk before deciding whether treatment is suitable and how closely you need to be monitored. For more see APOE genotyping.
Questions to ask your doctor
The choice of tests your doctor makes will be based on your medical history and symptoms. It is important that you tell them everything you think might help.
You play a central role in making sure your test results are accurate. Do everything you can to make sure the information you provide is correct and follow instructions closely.
Talk to your doctor about any medications you are taking. Find out if you need to fast or stop any particular foods or supplements. These may affect your results. Ask:
More information
Pathology and diagnostic imaging reports can be added to your My Health Record. You and your healthcare provider can now access your results whenever and wherever needed.
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