Alzheimer's: New strategy for amyloid diagnostics

Soon they will be authorized in Germany: the first drugs against Alzheimer's disease that are intended to slow down the progression of the condition. On November 14, 2024, the EMA granted approval for Lecanemab in the European Union. The drugs attack so-called amyloid plaques in the brain. But how can we reliably and cost effectively diagnose the presence of amyloid plaques in patients who show up at memory clinics with slight cognitive impairment or mild dementia -- that is, the target group for the drugs?

A new study by doctors at LMU University Hospital furnishes answers which could be incorporated into patient treatment. The study was initiated by Professor Matthias Brendel, Acting Director of the Department of Nuclear Medicine, Dr. Nicolai Franzmeier from the Institute for Stroke and Dementia Research, and Professor Günther Höglinger, Director of the Neurological Clinic -- all three of whom are also members of the SyNergy Cluster of Excellence. Now the results of the study have been published in the journal of the Alzheimer's Association, Alzheimer's & Dementia: Diagnosis, Assessment, & Disease Monitoring.

Which method is better?

Basically, there are two approved methods for identifying the presence of dangerous amyloid plaques in the brains of Alzheimer's patients. Method number 1 involves analyzing the patient's cerebrospinal fluid (CSF). However, this requires a spinal tap with a cannula -- an invasive procedure with rare complications. And for some patients, such as people on blood thinners, this test is unsuitable. Moreover, CSF analysis provides indirect, non-quantitative evidence of amyloid deposits in the brain.

Method number 2 involves a technique for imaging the brain called positron emission tomography (PET). This non-invasive method furnishes direct, semiquantitative evidence of amyloid deposits in the brain. At 1,500 to 3,000 euros per scan, however, the method is still prohibitively expensive and is not currently covered by health insurance plans. Depending on the equipment and expertise available in centers, moreover, the use of amyloid imaging and CSF analysis varies in Germany, with CSF analysis currently still more widespread.

To determine the diagnostic accuracy of the results of CSF tests compared to the gold standard PET imaging, the Munich researchers evaluated the data of over 400 patients with suspected Alzheimer's disease who were given both a CSF amyloid test and a PET scan of the brain at LMU University Hospital between 2013 and 2024.

The results showed that patients with amyloid values of over 7.1 in their CSF had PET scans that mostly did not pick up anything abnormal -- meaning they tested negative for Alzheimer's. Meanwhile, patients with amyloid values of less than 5.5 in their CSF predominantly had PET scans that showed up as abnormal as well -- meaning they tested positive for Alzheimer's with a high degree of probability. Most significantly, however, there was a gray area between 5.5 and 7.1 in the CSF -- concerning around 15 to 20 percent of patients. "Half of these study participants had abnormal amyloid results in their PET scans," says Brendel, "and so the CSF is not reliable enough here." In an independent patient cohort at the University of Vienna, the researchers obtained exactly the same outcome. Consequently, the results are robust.

Possible consequences for clinical practice

As soon as the new drugs for treating amyloid plaques are approved, the findings of the study could be incorporated into diagnostic practice. Amyloid PET would be the diagnostic method of choice where available. Depending on the expertise and equipment at a given location, however, many patients in Germany currently have readier access to CSF analysis than to amyloid PET. "From medical and economic standpoints, therefore, it seems reasonable to give these patients a CSF analysis in the first instance unless there are specific medical reasons to indicate otherwise," says Brendel.

This concerns around 70 to 80 percent of patients. "Of these patients, only those whose results are in the gray area between 5.5 and 7.1 would then need an additional PET scan. Matthias Brendel: "Especially if the costs of amyloid PET fall in future and broader access becomes possible, amyloid PET could become the first choice and avoid the duplication of effort and costs involved where two tests -- CSF and PET -- are currently required."