Biomarker Assessments Used to Test for Amyloid Beta


Jeffrey L. Cummings, MD, ScD, discusses the biomarker assessments used to test for amyloid beta that can confirm disease pathology for Alzheimer’s disease.

Jeffrey L. Cummings, MD, ScD: We’ve made tremendous progress in terms of the biomarkers for amyloidosis in the brain. That’s the basic pathology of Alzheimer’s disease. We have amyloid imaging, which allows us to see the amyloid plaque that’s in the brain. There are 3 approved versions of amyloid imaging, and all 3 of them give us basically the same information. You can also confirm the presence of amyloid by doing a lumbar puncture and looking in the CSF [cerebrospinal fluid] for reduced levels of the protein of amyloid, A beta 42. Why is it reduced in Alzheimer’s disease? Because it’s trapped in the plaque in the brain. As the plaque accumulates and becomes more obvious, the amyloid in the CSF goes down and becomes less obvious. You can also do ratios in the spinal fluid, such as the ratio of A beta 42 to tau, which reflects the ongoing tau pathology and neurofibrillary tangles in the brain. That ratio is a very good way to diagnose Alzheimer’s disease using the spinal fluid.

Amyloid imaging is appropriate to use in a variety of circumstances. First of all, it’s used to confirm the diagnosis of Alzheimer’s disease. Even the best clinicians are sometimes misled by the dementia syndrome that a patient has. They believe they have Alzheimer’s disease, but about 20% of cases that look like Alzheimer’s disease don’t have amyloid in the brain and aren’t Alzheimer’s disease. It can be used for confirmation of the diagnosis of Alzheimer’s disease. Because it isn’t reimbursed by CMS [Centers for Medicare & Medicaid Services], it’s rarely used for that because it’s an expensive type of imaging. If amyloidosis must be proven, it’s usually done with spinal fluid analysis.

Another circumstance in which amyloid imaging is very important is when the patient is a candidate for treatment with aducanumab [Aduhelm]. We must know that amyloid is in the brain before we expose the patient to aducanumab because aducanumab can have adverse effects that we wouldn’t want to expose the patient to unless they have the treatment’s target.

There are very few contraindications to the use of amyloid imaging. Because the imaging is done in a closed scanner, patients occasionally have some degree of claustrophobia and might not be able to tolerate the scanning. For spinal fluid, you have to do a lumbar puncture. If the patient has degenerative disease of the back, then it may be very hard for the clinician to place the needle easily to obtain the spinal fluid. It’s not exactly a contraindication, but it’s an important limitation. The only true contraindication for a lumbar puncture is if the patient is on an anticoagulant because they might hemorrhage around the puncture site and consequently put pressure on the spinal cord.

This transcript has been edited for clarity.

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