Differential diagnostic performance of a panel of plasma biomarkers for different types of dementia.
Level 3 - non-randomized controlled study
Cross-sectional multi-cohort diagnostic accuracy study comparing established clinical dementia groups.
PubMed 35603139 · doi:10.1002/dad2.12285
What was done
Plasma biomarkers (Aβ 1-42/1-40, p-tau181, neurofilament light [NfL], and glial fibrillary acidic protein [GFAP]) were measured via Simoa in two independent cohorts (cohort 1: n = 160; cohort 2: n = 152) to evaluate their ability to differentiate Alzheimer's disease (AD) dementia, frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). In one cohort, Aβ 1-42/1-40 was additionally quantified using mass spectrometry (MS). Optimal biomarker combinations were selected via logistic regression with Wald's backward elimination.
What was found
MS and Simoa Aβ 1-42/1-40 performed similarly in distinguishing AD from controls. For differentiating AD from FTD, the optimal Simoa panel included NfL and p-tau181 in cohort 1 (AUC = 0.94) and NfL, GFAP, and p-tau181 in cohort 2 (AUC = 0.90). For differentiating AD from DLB, the optimal panel was NfL, p-tau181, and GFAP in cohort 1 (AUC = 0.88) and p-tau181 alone in cohort 2 (AUC = 0.81). Plasma Aβ 1-42/1-40 did not improve discrimination among the dementia subtypes.
Why it matters
Blood-based biomarkers combining p-tau181 with markers of neurodegeneration (NfL) and astrogliosis (GFAP) can assist in the differential diagnosis of AD versus FTD and DLB without requiring invasive lumbar punctures or PET imaging.
Limits
The optimal panel components differed between cohorts (GFAP contributed to AD vs FTD only in cohort 2, and to AD vs DLB only in cohort 1). The abstract lacks group-specific sample sizes, sensitivity, specificity, confidence intervals, and reference-standard diagnostic criteria (e.g., clinical vs neuropathological validation).
Cited by
- supports A biomarker profile of normal p-tau, normal GFAP, and elevated neurofilament light (NfL) in blood is commonly associated with frontotemporal dementia.