Diagnostic evaluations of dementia increasingly involve fluid biomarker analysis. Current diagnostic criteria for Alzheimer’s disease (AD) allow the diagnosis to be established solely on the basis of abnormal cerebrospinal fluid (CSF) or plasma levels of specific amyloid β (Aβ) and phosphorylated tau (p-tau) species, even in the absence of overt clinical symptoms. ^{Reference Jack, Andrews and Beach1} Although dementia with Lewy bodies (DLB) remains fundamentally a clinical diagnosis, CSF α-synuclein biomarkers have also gained attention as a potential supportive tool for diagnosis. ^{Reference McKeith, Boeve and Dickson2,Reference McKeith, Ferman and Thomas3} Importantly, while distinct dementia syndromes are canonically associated with specific underlying pathologies, mixed pathology is common in the real world. ^{Reference Schneider, Arvanitakis, Bang and Bennett4} Thus, it is critical to better understand how fluid biomarkers apply to various types of dementias and their potential utility for differential diagnosis. Equally important is linking fluid biomarkers to specific clinical manifestations that may emerge in dementia. Although neurodegenerative diseases such as AD may be diagnosed based solely on biological markers, it is the emergence and progression of clinical symptoms that ultimately matter most to patients and caregivers.

The study by Oliveira et al. ^{Reference Oliveira, Miraldo and Castro-Net5} examined associations between multiple CSF biomarkers and motor and non-motor clinical features in a cohort of 81 patients with DLB, AD or healthy controls recruited from Hospital São Paulo in Brazil. Participants were further stratified by apolipoprotein E ϵ4 (APOE-ϵ4) carrier status. In DLB, APOE-ϵ4 non-carriers exhibited worse functional and more severe non-motor symptoms, alongside lower tau and higher ubiquitin and neurofilament light levels. Several clinical measures in DLB, including sleep disturbances, functional status and motor symptoms, were associated with amyloid, tau, α-synuclein and ubiquitin biomarkers. In contrast, in AD, motor symptom severity was only associated with ubiquitin levels. Overall, these findings highlight syndrome-specific relationships between fluid biomarkers and clinical manifestations, particularly when APOE-ϵ4 carrier status is taken into account.

The work is consistent with, and extends, prior studies demonstrating the potential utility of CSF biomarkers for differential diagnosis across dementia syndromes. ^{Reference Hansson, Hall and Öhrfelt6} By explicitly linking biomarker profiles to distinct clinical features, the study furthers our understanding of how molecular pathologies may contribute to symptom expression. However, the relatively small sample size and cross-sectional design limit the generalizability and causal interpretation of the findings. Future studies with larger samples and longitudinal study designs are required to clarify how specific pathological processes drive clinical manifestations, which may ultimately inform more precise diagnosis, prognostication and targeted therapeutic strategies.