A blood biomarker test for brain amyloid impacts the clinical evaluation of cognitive impairment

Abstract

ObjectiveThe objective of this study was to examine clinicians' patient selection and result interpretation of a clinically validated mass spectrometry test measuring amyloid beta and ApoE blood biomarkers combined with patient age (PrecivityAD® blood test) in symptomatic patients evaluated for Alzheimer's disease (AD) or other causes of cognitive decline.MethodsThe Quality Improvement and Clinical Utility PrecivityAD Clinician Survey (QUIP I, ClinicalTrials.gov Identifier: NCT05477056) was a prospective, single‐arm cohort study among 366 patients evaluated by neurologists and other cognitive specialists. Participants underwent blood biomarker testing and received an amyloid probability score (APS), indicating the likelihood of a positive result on an amyloid positron emission tomography (PET) scan. The primary study outcomes were appropriateness of patient selection as well as result interpretation associated with PrecivityAD blood testing.ResultsA 95% (347/366) concordance rate was noted between clinicians' patient selection and the test's intended use criteria. In the final analysis including these 347 patients (median age 75 years, 56% women), prespecified test result categories incorporated 133 (38%) low APS, 162 (47%) high APS, and 52 (15%) intermediate APS patients. Clinicians' pretest and posttest AD diagnosis probability changed from 58% to 23% in low APS patients and 71% to 89% in high APS patients (p < 0.0001). Anti‐AD drug therapy decreased by 46% in low APS patients (p < 0.0001) and increased by 57% in high APS patients (p < 0.0001).InterpretationThese findings demonstrate the clinical utility of the PrecivityAD blood test in clinical care and may have added relevance as new AD therapies are introduced.

Highly accurate blood test for Alzheimer’s disease is similar or superior to clinical cerebrospinal fluid tests

“…Despite BBMs being used in clinical practice in some countries, including the United States, they have not been recommended as standalone diagnostic tests due to a lack of studies demonstrating their equivalence to clinically used CSF and PET methods 16 , 35 – 37 . Therefore, we compared the diagnostic performance of plasma %p-tau217 with clinically used and FDA-approved CSF assays (CSF Aβ42/40 from Fujirebio and p-tau181/Aβ42 from Roche) in independent Swedish and US cohorts.…”

Effect of Neprilysin Inhibition on Alzheimer Disease Plasma Biomarkers

“…In AD, this ratio is only reduced by 8% to 14%, 3 while sacubitril/valsartan reduces it by approximately 30%. Given the frequent co-occurrence of heart disease and cognitive impairment and increasing clinical availability of plasma Aβ42/Aβ40 tests, 5 results for patients receiving sacubitril/valsartan should be interpreted cautiously; treatment-related Aβ42/Aβ40 reductions may lead to false-positive results and misclassification of Aβ positivity as being AD. This drug interaction contraindication for an AD blood test underscores the importance of considering potential confounders, especially in patients with comorbidities, such as for p-tau and kidney disease, 6 and suggests that a multibiomarker assessment may better control for factors affecting individual biomarker classes.…”

Biological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals

“…Plasma Aβ42/Aβ40 is a widely investigated biomarker associated with Aβ pathology currently in clinical use to support an AD diagnosis. 12,67,68 However, in Aβ-positive versus Aβ-negative individuals, plasma Aβ42/Aβ40 is only decreased by 8% to 14%. 13 This clinical context places, per se, an issue for this biomarker, because the modest disease-related fold changes are in a similar magnitude to that of common analytical variation figures seen in clinical chemistry.…”