Reconsidering white matter vulnerability and biomarker interpretation across Lewy body dementia subtypes

作者：Shuo Liu, Siwen Yang, Yi Sui · 发表于：Alzheimer s & Dementia · 年份：2025 · DOI：10.1002/alz.70566 · 被引用次数：1 · 研究领域：Neurological Disease Mechanisms and Treatments、Alzheimer's disease research and treatments、Neuroinflammation and Neurodegeneration Mechanisms

To the Editor, We read with interest the recent article by Hannaway et al. entitled “Neuroimaging and plasma biomarker differences and commonalities in Lewy body dementia subtypes.”1 This study used advanced fixel-based diffusion imaging and plasma biomarker profiling to delineate both shared and distinct pathophysiological features across dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). The authors’ multimodal approach provides valuable insights into white matter alterations and fluid markers underlying cognitive heterogeneity in Lewy body dementia (LBD). Building on these findings, we would like to offer some further reflections from a clinical translational perspective that may help refine mechanistic interpretation and therapeutic implications. First, while both DLB and PDD are unified under the umbrella of LBD, their distinct profiles of white matter microstructural integrity—particularly the more pronounced fiber density (FD) reductions in PDD—suggest potential differences in underlying pathophysiology beyond alpha-synuclein deposition alone. The authors’ finding that these differences occurred despite comparable levels of plasma neurofilament light chain (NfL) and phosphorylated tau217 (p-tau217) suggests the presence of alternative contributors to white matter vulnerability in PDD. In clinical settings, patients with PDD often present with a longer duration of parkinsonian symptoms prior to cognitive decline, raising the possibility that chronic...