⚙
AI-generated deep summary
by claude@2026-07, 2026-07-16
· read from full text
ⓘ
The study used the NULISA CNS multiplex proteomics panel to analyze 852 baseline and longitudinal cerebrospinal fluid (CSF) samples from controls, PD without cognitive impairment (PD-NCI), PD with cognitive impairment (PD-CI), dementia with Lewy bodies (DLB), and Alzheimer’s disease (AD), with a subset additionally tested by alpha-synuclein seed amplification assay (αSyn-SAA). Among 124 panel markers, 53 were significantly altered in PD-CI and/or DLB versus controls, with 12 showing divergent abundance trends between LBD-associated targets and AD. Alpha-synuclein measured by NULISA did not change across clinical LBD diagnoses, but differed in subgroup comparisons of SAA+ versus SAA− cases, and longitudinal analyses identified five proteins whose baseline levels tracked with later cognitive progression. Machine learning using sets of 10 markers achieved high accuracy for discriminating clinical diagnoses and SAA positivity (AUC > 0.89). This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
Lewy body dementia (LBD), which encompasses Parkinson’s disease dementia (PDD) and Dementia with Lewy bodies (DLB), lacks established biofluid markers of its complex clinical and neuropathological heterogeneity. Multiplex proteomic tools, such as the recently developed NUcleic acid Linked ImmunoSandwich Assay (NULISA TM ), can assess a diverse array of neurodegenerative targets and address these biomarker gaps. We used this platform to analyze 852 baseline and longitudinal cerebrospinal fluid (CSF) samples from control, PD, and DLB subjects from the Parkinson’s Disease Biomarker Program (PDBP). We then examined LBD protein signatures across different clinical diagnoses, patterns of cognitive progression, and underlying neuropathologies. Of the 124 markers analyzed, 54 were significantly altered in PD with cognitive impairment and/or DLB compared to controls, many serving as informative clinical classifiers in machine learning models. We also identified 15 proteins with significant baseline and/or longitudinal changes linked to cognitive progression. To identify neuropathological signatures, we stratified 209 cases by the presence of underlying synuclein and amyloid-beta (Aβ) pathology using CSF alpha-synuclein seed amplification assay (αSyn-SAA) results and NULISA pTau-217 levels, respectively. Select synaptic markers were decreased relative to synucleinopathy but increased relative to Aβ accumulation, complicating their interpretation in cases with co-pathology. These neuropathological analyses were replicated in an independent cohort of 917 cases from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Overall, these results highlight the utility of multiplex proteomic analysis in the identification of candidate CSF biomarkers of disease heterogeneity in LBD. One Sentence Summary This multiplex proteomic analysis using the recently released NULISA platform revealed unique targets of Lewy body dementia progression and neuropathology.
Full text
1,978 characters
· extracted from
oa-doi-fallback
· click to expand
Abstract
Lewy body dementia (LBD), which encompasses Parkinson’s disease dementia (PDD) and Dementia with Lewy bodies (DLB), currently lacks established biofluid markers reflective of its complex molecular pathophysiology. Multiplex proteomic tools, such as the recently released NUcleic acid Linked ImmunoSandwich Assay (NULISATM), can simultaneously assess a diverse array of neurodegenerative targets and address this critical biomarker gap. We used the NULISA CNS disease panel to analyze 852 baseline and longitudinal cerebrospinal fluid (CSF) samples from control, PD without cognitive impairment (PD-NCI), PD with cognitive impairment (PD-CI), DLB, and Alzheimer’s disease (AD) subjects. A subset of control and DLB cases also had alpha-synuclein seed amplification assay (αSyn-SAA) results. Of the 124 panel markers analyzed, nearly half (n=53) were significantly altered in PD-CI and/or DLB compared to controls. Of these LBD-associated targets, 12 demonstrated divergent abundance trends in AD. Alpha-synuclein (SNCA) as measured by NULISA did not change across clinical LBD diagnoses but was among proteins significantly altered in subgroup comparisons of SAA+ and SAA-cases. Longitudinal analysis revealed five proteins (NEFL, NRGN, CCL26, CRH, PGF) with baseline changes indicative of subsequent cognitive progression. Machine learning identified a series of panels, each comprising only 10 markers, capable of discriminating clinical diagnoses and SAA positivity with high accuracy (AUC > 0.89). Overall, our results highlight the utility of NULISA multiplex proteomic analysis in the identification of diagnostic and prognostic CSF biomarkers of LBD that reflect its diverse molecular pathophysiology.
One Sentence Summary This multiplex proteomic analysis using the recently released NULISA platform revealed unique targets of Lewy body dementia pathology and progression.
Competing Interest Statement
A.I.L, N.T.S., and D.M.D. are co-founders of Emtherapro Inc.
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.