Tau/Aß42

What is being measured?
Amyloid beta 42 (Aß42) is a peptide whose production can be increased in the brain and which is deposited in structures called senile plaques. Tau, on the other hand, is a structural protein of the brain that, when chemically modified (loaded with phosphate groups, P-tau), can form what are called neurofibrillary tangles: twisted protein fragments inside neurons that destroy their ability to transmit signals.

The presence of these tangles together with plaques at post-mortem is considered the main diagnostic sign of Alzheimer’s disease. Measurement of Aß42 and tau in CSF is being evaluated for its potential role in diagnosing and monitoring Alzheimer’s disease. It has been shown that a decrease in Aß42 combined with high levels of tau or P-tau may predict the onset of Alzheimer’s disease.

How is the sample collected for testing?
Cerebrospinal fluid samples are collected by a procedure called lumbar puncture (“spinal tap”). This procedure is usually carried out in a hospital or clinic

Is any test preparation needed to ensure the quality of the sample?
Your doctor will tell you about any preparation required. This is not a blood test but a test on cerebrospinal fluid. Lumbar punctures are usually carried out in hospital.

How is it used?
Tau protein and Aß42 tests may be used as additional tests to help diagnose Alzheimer’s disease.

If a person has symptoms of dementia, such as memory loss, changes in behaviour and a reduced ability to carry out everyday activities, the doctor will carry out a full assessment to try to find the cause. This assessment may include a series of cognitive tests (Mini-Mental State Examination) to assess memory and possibly PET scans (Pittsburgh Compound-B) of the brain to look for abnormalities.

When is it requested?
Tau protein and Aß42 tests are mainly performed in research protocols and in some specialist memory clinics, together with cognitive tests and brain scans. Some doctors may request them outside these protocols; however, information on how to interpret the results is limited.

What does the result mean?
In a patient with symptoms, a low level of Aß42 in the cerebrospinal fluid together with a high level of tau reflects an increased likelihood of Alzheimer’s disease. Recent studies have shown that these abnormal values can predict rapid progression of Alzheimer’s disease. Because these tests are still at the research stage and are not part of routine testing, it is not yet clear whether everyone with abnormal results will definitely develop Alzheimer’s disease.

What else should I know?
Aß42 and tau protein measurements do not establish a diagnosis of Alzheimer’s disease on their own; abnormal findings are fairly common, so they should be used together with other tests and with the patient’s medical and family history to suggest a diagnosis of Alzheimer’s disease.

The clinical use of these tests is constantly evolving. For example, multiple variants of the beta-amyloid protein, such as Aß40 and Aß38, have been identified and are being studied for their potential use as biological markers of Alzheimer’s disease.

How is Alzheimer’s disease definitively diagnosed?
The diagnosis of Alzheimer’s disease is currently based on observing cognitive changes and ruling out other causes of these changes. The disease is definitively confirmed after death by looking for the microscopic changes that occur in the affected person’s brain tissue. This requires microscopic examination of the number of senile plaques and neurofibrillary tangles found in the brain.

Characteristic changes on brain scans (magnetic resonance imaging and positron emission tomography) and/or low levels of Aß42 and high levels of tau protein in the cerebrospinal fluid (when available) may be requested to help make the diagnosis

Can the test be done on my blood instead of cerebrospinal fluid?
Not at present. Studies measuring Aß42 and tau protein in blood have shown that they are not useful indicators of what is happening inside the brain.