Plasma biomarker levels change in differing ways for different types of early-onset dementia, with unique clinical associations that could help stratify risk in patients, research suggests.
The findings may help improve detection and prognosis of these neurodegenerative diseases, which manifest before the age of 65 years and are often challenging to treat due to atypical symptoms and clinical heterogeneity.
The report, in JAMA Network Open, revealed differences in both the concentrations of biomarkers over time and their association with clinical outcomes in early-onset Alzheimer disease (EOAD) and frontotemporal dementia (FTD).
“Our results highlight disease-specific plasma biomarker dynamics and their potential utility in monitoring disease progression in early-onset dementia,” reported Eun-Joo Kim, PhD, from Pusan National University Hospital in Korea, and colleagues.
Recent developments with plasma biomarkers have changed the landscape of dementia diagnosis.
Phosphorylated tau 217 (p-tau217), a marker specific of Alzheimer’s disease, has been found to be highly accurate in detecting its pathology.
Meanwhile, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are emerging as astrocytic activation and neurodegeneration markers, respectively, with NfL particularly relevant for FTD.
Combining p-tau217 and NfL could therefore enable Alzheimer’s disease and FTD, two leading causes of dementia at an early age, to be distinguished.
To investigate further, Kim and team compared biomarker trajectories and clinical outcomes in 322 patients with EOAD and FTD, of whom 245 had EOAD and 77 FTD.
Around two thirds of each group was female, and the mean age was in the early to mid 60s.
High baseline levels of p-tau217, GFAP, and NfL were significantly associated with all clinical outcomes in the EOAD group, assessed using scores on the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating–Sum of Boxes (CDR-SB).
However, among patients with FTD, only baseline GFAP and NfL were associated with decreases in MMSE scores.
The association of p-tau217 and GFAP levels with clinical outcomes was greater at earlier stages of EOAD, with the former biomarker showing no association at later stages of disease.
The plasma biomarkers followed distinct longitudinal trajectories in the two forms of early-onset dementia. In the EOAD group, the levels of all three biomarkers increased significantly over time, but with FTD only NfL increased.
Annualized changes in levels of all three biomarkers showed outcome-specific associations with clinical decline in EOAD. GFAP and NfL changes were associated with declines in MMSE score and p-tau217 levels with worsening CDR-SB score in this group. No such associations were observed for patients with FTD.
“In this multicenter, prospective cohort study of patients with EOAD and FTD, the clinical relevance of plasma biomarker levels and longitudinal changes may vary between EOAD and FTD,” the authors summarized.
“These findings may inform future clinical practice and trial design regarding stratifying patient populations and monitoring clinical progression, particularly in EOAD.”
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