Faculty, Staff and Student Publications

Language

English

Publication Date

7-6-2026

Journal

NeuroImage: Clinical

DOI

10.1016/j.nicl.2026.104033

PMID

42442132

PMCID

PMC13382092

PubMedCentral® Posted Date

7-6-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Aim: Despite the intimate link between cerebral blood flow (CBF) alterations and Parkinson's disease (PD) pathogenesis and cognitive decline, the precise pathophysiological mechanisms driving this relationship remain elusive. This study seeks to correlate changes in CBF with regional gene expression to advance mechanistic understanding of the disease.

Methods: CBF group differences were first determined from ASL data in 53 PD and 40 healthy controls (HC) and subsequently correlated with cognitive scores (Dataset 1). A coordinate-based meta-analysis of published literature provided a second set of CBF differences (Dataset 2). Transcriptomic data from the Allen Human Brain Atlas were then correlated with hemodynamic patterns derived from each dataset to identify genes associated with CBF alterations across two independent datasets. The statistically significant genes from each cohort were intersected to obtain a common gene set, which subsequently underwent functional annotation and cell-type enrichment analysis. Finally, cross-modal spatial correlation was employed to investigate CBF changes associated with neurotransmitters.

Results: In dataset 1, PD showed decreased CBF in frontal and occipital regions, but increased CBF in limbic and parietal areas. CBF variations in the hippocampus, parahippocampal gyrus, and postcentral gyrus correlated with cognitive scores (MMSE/MoCA). Dataset 2 revealed frontal region and angular gyri hypoperfusion. Integration with transcriptomic data identified an overlapping gene set, enriched in synaptic structure, plasticity, and energy metabolism pathways. Cellular enrichment showed predominant expression in excitatory/inhibitory neurons, microglia, and oligodendrocyte precursor cells. Neurotransmitter association analysis linked CBF alterations to the norepinephrine transporter (NET).

Conclusion: By integrating transcriptomic and neuroimaging findings, this study suggests that CBF alterations may be linked to specific genes and biological processes in PD.

Keywords

Parkinson's disease, Cerebral blood flow, Cognitive function, Gene expression, Enrichment analysis

Published Open-Access

yes

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