Biology subjects

Dobreva, I.

Publications and source records attributed to Dobreva, I..

5 recordsLinked to original sources

bioRxiv2026

Grey matter microstructural alterations distinguish cognitive impairment in Lewy body diseases

INTRODUCTION.Despite widespread cortical involvement in Lewy body diseases, conventional grey matter MRI measures have limited sensitivity. Microstructural measures from diffusion MRI may be more sensitive to early changes. METHODS.We examined grey matter microstructure in 197 participants across the Lewy body diseases spectrum: 88 Lewy body dementia (LBD), 109 Parkinsons normal cognition (PD-NC), and 46 controls. We compared tissue-weighted neurite density (tNDI), orientation dispersion index (tODI), and free water fraction (FWF) cross-sectionally and longitudinally. We examined relationships between microstructure, disease severity and plasma p-tau217. RESULTS.LBD participants showed widespread cortical and subcortical tODI and FWF increases compared to controls and PD-NC, despite minimal atrophy. These changes correlated with cognitive (but not motor severity) and with p-tau217. In 100 Parkinsons patients followed-up over 3 years, cortical FWF increased in those developing cognitive decline. DISCUSSION.Microstructural measures capture early grey matter changes, offering a sensitive marker of grey matter integrity in Lewy body diseases.

neuroscience↗

bioRxiv2025

Mapping the molecular landscape of the living brain: integrating spatial transcriptomics and qMRI

Profiling dynamic molecular processes in neurodegeneration in vivo remains a major clinical challenge. Limited brain tissue accessibility especially limits the development and effective deployment of emerging disease modifying therapies, highlighting the need for non-invasive methods for profiling molecular disease processes. We introduce a non-invasive imaging framework that integrates ultra-high-resolution 7T quantitative MRI (qMRI) with spatially-resolved transcriptomics (SRT) to infer cell-type and pathway-specific molecular features within the cortical grey matter. This proof-of-concept establishes the integration of qMRI and SRT as a scalable, non-invasive platform for molecular profiling in neurodegeneration, with significant potential for precision therapeutic monitoring, drug development and clinical trials.

neuroscience↗

bioRxiv2025

Evidence for divergent cortical organisation in Parkinsons disease and Lewy Body Dementia

Dementia is a defining feature of Lewy body disease: its timing and onset distinguish different clinical diagnoses, and its effect on quality of life is profound. However, it remains unclear whether processes leading to cognitive and motor symptoms in Lewy body disease differ. To clarify this, we used in-vivo neuroimaging to assess spatial gradients of inter-regional differences in structural and functional connectivity in 108 people across the Lewy body disease spectrum (46 Parkinsons with normal cognition (PD-NC), 62 Lewy body dementia (LBD)) and 23 controls. We found divergent structural gradient differences with cognitive impairment: PD-NC showed increased inter-regional differentiation, whilst LBD showed overall gradient distribution similar to controls despite widespread organisational differences at the regional level. We then assessed cellular and molecular underpinnings of these organisational changes. We reveal similarities and also important differences in the drivers of cortical organisation between LBD and PD-NC, particularly in layer 4 excitatory neurons.

neuroscience↗

bioRxiv2025

Neuroimaging and plasma biomarker differences and commonalities in Lewy body dementia subtypes

INTRODUCTIONDespite ongoing debate about whether Parkinsons disease dementia (PDD) and dementia with Lewy bodies (DLB) are separable diseases or a single Lewy body dementia (LBD) spectrum, there are limited neuroimaging investigations of differences between these conditions. METHODSWe used fixel-based diffusion MRI and plasma measures to examine white matter integrity and burden of amyloid pathology (using tau phosphorylated at theonine-217 (p-tau217) in 47 patients with DLB, 21 PDD, 29 PD and 23 age-matched controls. RESULTSWe show reduced fibre cross-section in LBD versus PD, and increased concentrations of plasma neurofilament light chain and p-tau217; with p-tau217 and fibre cross-section associated with cognition. Fibre density was reduced in PDD versus DLB, but neither plasma measures nor fibre cross-section differed between LBD subtypes. DISCUSSIONOur findings suggest differences in white matter integrity between DLB and PDD that are driven by distinct processes from those causing changes in white matter integrity in LBD compared with PD.

neuroscience↗

bioRxiv2025

Impaired glymphatic clearance independently contributes to poor outcomes in Parkinsons disease

BackgroundImpaired glymphatic clearance may contribute to pathological accumulations in Parkinsons (PD), but how it interacts with other processes causing dementia and poor outcomes remains unclear. ObjectivesClarify how glymphatic clearance impacts cognition in PD and its interaction with established imaging markers. MethodsWe used diffusion tensor image analysis along the perivascular space (DTI-ALPS) as an indirect marker of glymphatic clearance in 98 PD patients (31 PD-poor outcomes: dementia, mild cognitive impairment, frailty or death within 3-year follow-up; 67 PD-good outcomes) and 28 controls. We assessed DTI-ALPS relationship to cognition, white matter (fibre cross-section), cortical thickness, iron accumulation (quantitative susceptibility mapping (QSM)), and plasma markers (phosphorylated tau-181 (p-tau181 and neurofilament light (NFL)) cross-sectionally and longitudinally. ResultsDTI-ALPS was lower in PD-poor outcomes compared to PD-good outcomes and controls (p=0.005) with further longitudinal reductions only in PD-poor outcomes (group*time interaction: {beta}=-0.013, p=0.021). Lower DTI-ALPS was associated with lower fibre cross-section in P, at baseline and longitudinally but with different spatial distribution from white matter changes relating to PD cognition. There was no correlation between baseline DTI-ALPS and plasma ptau-181 (p=0.642), NFL (p=0.448) or baseline cortical thickness. Lower DTI-ALPS was associated with accelerated cortical thinning within left precentral gyrus and changes in brain iron distribution. ConclusionsPD patients who develop poor outcomes show impaired glymphatic clearance at baseline that worsened longitudinally. DTI-ALPS correlated with white matter integrity and brain iron accumulation. However, both showed different spatial distribution than that seen in PD dementia; suggesting impaired glymphatic clearance contributes to cognitive decline in a distinct manner.

neuroscience↗