With the availability of imaging and fluid biomarkers, such as the amyloid positron emission tomography (PET) scan and cerebrospinal fluid analysis, and with the recent US Food and Drug Administration (FDA) clearance of the first blood-based biomarker test, physicians now have more diagnostic tools for AD to complement their clinical assessment.

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The new blood-based biomarker measures the ratio of 2 plasma proteins: p-tau217, which is a sensitive measure of amyloid burden, and b-amyloid (Aβ)1-42, which is the toxic form of Aβ. In a recent study, this test demonstrated a positive predictive value of almost 92% and a negative predictive value of more than 97%. So, the test is highly sensitive and specific, and it is much less intrusive than an amyloid PET scan or a spinal tap to collect cerebrospinal fluid. It is worth mentioning that up to 20% of those who get this blood test will have indeterminate results that are not clearly positive or negative. Those individuals will have to get an amyloid PET scan for confirmation.

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In many parts of the country, patients have to travel a long distance to see an expert for an AD evaluation, and there also could be a long wait to see the expert and to get the amyloid PET scan and spinal tap. This blood-based biomarker test will help to democratize the process of biomarker evaluation and is anticipated to shorten the time to diagnosis. There are several other blood-based biomarker tests for AD that are also under investigation, including tests that measure %p-tau217 and Aβ42/40, and we expect that they will be similarly sensitive and specific.

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Newer treatments for AD include the disease-modifying therapies lecanemab and donanemab, which target Aβ plaques. Lecanemab is given by infusion every 2 weeks for the first 18 months, and then you can go on maintenance therapy every 2 weeks or once a month. Lecanemab is associated with infusion reactions in approximately 25% of people, and approximately 12.5% develop amyloid-related imaging abnormalities (ARIA). Most treated individuals with AD who develop ARIA have no clinical symptoms, so magnetic resonance imaging scans at regular intervals are necessary. Donanemab is infused every 4 weeks, and, in phase 3 trials, it was associated with a higher frequency of ARIA and a lower risk of infusion reactions than lecanemab. Donanemab treatment stops when you have cleared out the brain Aβ, as demonstrated in an amyloid PET scan.

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There are other amyloid antibodies under investigation that either have higher binding specificities or use different brain shuttle technologies or binding sites. We are hoping that they will be faster in terms of clearing out Aβ and that they will have a lower risk of side effects. Moreover, there are some amyloid antibodies that may be easier to use and can be given subcutaneously, maybe only once every couple of months. We are also developing tau- and neuroinflammation-targeting antibodies and small molecules, as well as drugs that target metabolic derangements, which may be some of the most intriguing investigational therapies.