Plasma biomarkers for Alzheimer’s disease: a field-test in a memory clinic

Abstract

BackgroundThe key Alzheimer’s disease (AD) biomarkers are traditionally measured with techniques/exams that are either expensive (amyloid-positron emission tomography (PET) and tau-PET), invasive (cerebrospinal fluid Aβ42and p-tau181), or poorly specific (atrophy on MRI and hypometabolism on fluorodeoxyglucose-PET). Recently developed plasma biomarkers could significantly enhance the efficiency of the diagnostic pathway in memory clinics and improve patient care. This study aimed to: (1) confirm the correlations between plasma and traditional AD biomarkers, (2) assess the diagnostic accuracy of plasma biomarkers as compared with traditional biomarkers, and (3) estimate the proportion of traditional exams potentially saved thanks to the use of plasma biomarkers.MethodsParticipants were 200 patients with plasma biomarkers and at least one traditional biomarker collected within 12 months.ResultsOverall, plasma biomarkers significantly correlated with biomarkers assessed through traditional techniques: up tor=0.50 (p<0.001) among amyloid,r=0.43 (p=0.002) among tau, andr=−0.23 (p=0.001) among neurodegeneration biomarkers. Moreover, plasma biomarkers showed high accuracy in discriminating the biomarker status (normal or abnormal) determined by using traditional biomarkers: up to area under the curve (AUC)=0.87 for amyloid, AUC=0.82 for tau, and AUC=0.63 for neurodegeneration status. The use of plasma as a gateway to traditional biomarkers using cohort-specific thresholds (with 95% sensitivity and 95% specificity) could save up to 49% of amyloid, 38% of tau, and 16% of neurodegeneration biomarkers.ConclusionThe implementation of plasma biomarkers could save a remarkable proportion of more expensive traditional exams, making the diagnostic workup more cost-effective and improving patient care.

Blood biomarkers: ready for clinical practice?

“…However, we require real-world blood biomarker data before validating them for clinical use. 5 6 To this end, here, we present three papers that illuminate the practical application of blood biomarkers-Altomare et al 7 (Geneva Cohort) and Lehman et al 8 (BALTAZAR cohort) assess the performance of AD blood biomarkers in memory clinics, and Veria et al 9 highlight potential for positive AD blood biomarkers in amyotrophic sclerosis.…”

The impact of tau deposition and hypometabolism on cognitive impairment and longitudinal cognitive decline

“…Blood-based biomarkers might likely be more useful during the earliest stages, where phospho-tau can predict future increases in tau-PET 66,67 and can play a key role in prescreening subjects for further neuroimaging examinations. 68 In this context, the use of plasma as a gateway to traditional biomarkers could avoid additional investigations in relevant proportions of cases, making the diagnostic workup more cost-effective and improving patient care. 68 There are some limitations and strengths to this study.…”

“…68 In this context, the use of plasma as a gateway to traditional biomarkers could avoid additional investigations in relevant proportions of cases, making the diagnostic workup more cost-effective and improving patient care. 68 There are some limitations and strengths to this study. First, we used MMSE as a measure of cognitive decline, although we are aware that MMSE is a global measure characterized by a ceiling effect, less sensitive than other tests or test combinations.…”

The potential clinical value of plasma biomarkers in Alzheimer's disease

“…Clinical utility will also need to be established; the plasma biomarker test will need to have a positive impact on patient management to secure future reimbursement and wide‐scale adoption. In a field‐test study conducted in a memory clinic, plasma biomarkers demonstrated excellent diagnostic accuracy compared to current confirmatory diagnostic tests (MRI, PET, and CSF biomarker analysis); it was estimated that plasma biomarker testing reduced the number of confirmatory diagnostic tests needed by up to 49%, highlighting their potential clinical utility as diagnostic tools 72 …”

“…In a field-test study conducted in a memory clinic, plasma biomarkers demonstrated excellent diagnostic accuracy compared to current confirmatory diagnostic tests (MRI, PET, and CSF biomarker analysis); it was estimated that plasma biomarker testing reduced the number of confirmatory diagnostic tests needed by up to 49%, highlighting their potential clinical utility as diagnostic tools. 72 Implementation studies should be undertaken to gather evidence on how plasma biomarker testing can be incorporated in various different clinics and contexts and to examine the most effective ways to use plasma biomarker testing in clinical settings. The expectation is that this will vary depending on the type of clinic and the standard of care within the clinic or geographical region in question but more research is needed.…”