Blood-based biomarkers for dementia with Lewy bodies

Abstract

Dementia with Lewy bodies (DLB), a synucleinopathy, is the second most common form of dementia after Alzheimer's disease (AD). Yet, DLB is often more aggressive and clinically challenging to diagnose due to overlapping symptoms with AD and Parkinson's disease dementia. Reliable biomarkers are necessary, since a definitive diagnosis of DLB currently requires postmortem tissue analysis. Blood-based biomarkers represent a minimally invasive and cost-effective avenue for earlier and more accurate diagnosis. This review integrates current evidence on blood biomarkers for DLB, at times extrapolated from other synucleinopathies, with a focus on α-synuclein and its derivatives, including extracellular vesicle-associated α-synuclein, seeding amplification assays, and autoantibodies. Additional biomarkers such as phosphorylated tau and amyloid-β highlight the frequent co-pathology with AD, while markers of neurodegeneration, neuroinflammation, and oxidative stress, heart-type fatty acid-binding protein, proteomic profiling, lipid, and other metabolites offer complementary diagnostic and prognostic potential. Although no single blood biomarker currently provides definitive diagnostic, differential, and prognostic accuracy for DLB, the studies reviewed here provide converging evidence that combined blood-based biomarker panels may offer meaningful clinical promise in facilitating earlier detection, guiding prognosis, and improving the design of targeted therapeutic trials for DLB.