Amyloid blood testing could cause 50% drop in PET scans required for Alzheimer’s trials

Blood tests used to detect damaging brain conditions such as concussions or Alzheimer’s disease are eliminating the need for some medical imaging exams. And new testing to screen for amyloid-beta may threaten to cut PET scan use by 50% in Alzheimer’s research trials.

That’s according to a study of more than 400 dementia-free British participants with an average age of 71, published last week in Brain. Researchers compared three different techniques to determine how well each predicted a positive cortical 18F-florbetapir amyloid PET scan.

Mass spectrometry plasma tests performed better than all other measures at discerning amyloid PET and consistently reduced the number of asymptomatic people who would need to undergo amyloid PET scans, corresponding author Jonathan M. Schott, MD, with University College London, and colleagues explained.

“Using either liquid chromatography [or] mass spectrometry method[s] to screen before PET scanning has the potential to yield significant savings for clinical trial recruitment, affording further reductions in the required number of PET scans compared to the number of scans needed without pre-screening or when using age, sex and APOE ε4 carrier status for screening,” the authors wrote Jan. 22.

For their investigation, Schott et al. compared liquid chromatography, mass spectrometry measures of plasma amyloid-beta, and single-molecule array (Simoa) measures of plasma amyloid-beta and phosphorylated tau181 (phospho-tau181). Each approach was tested in dementia-free individuals from Insight46, a sub-study of British citizens born in 1946.

Overall, the cohort included 441 adults. About 51% were women and 18.6% were amyloid PET-positive. Mass spectrometry plasma testing beat out all other measures. And across theoretical ranges of amyloid PET positivity prevalence of 10% to 50%, it routinely reduced the number of people who would have received a PET scan.

Building off this finding, if the group wanted to identify 100 amyloid PET-positive, dementia-free adults among a cohort similar to the one used in this study, they would need to perform 543 PET scans. With mass spectrometry plasma amyloid-beta testing, however, 623 would need a blood test, with only 243 going on to receive a scan, the authors wrote.

“In addition to cost reduction, plasma testing may allow for screening of more diverse populations at scale, and reductions in screen failures, resulting in faster clinical trial recruitment,” Schott et al. added.

The study was limited by its use of white and British patients and may not be relevant to more diverse populations, the group explained. Despite this, there is a clear path forward for using amyloid blood tests in Alzheimer’s trials.

“Our study strengthens a growing body of evidence that plasma screening can reduce the numbers of amyloid PET scans required to identify amyloid-β-positive individuals, for recruitment to clinical trials or ultimately for giving anti-amyloid therapies, and suggests that this may be feasible in a preclinical cohort,” the group concluded.