ArticleScientific reports2022
Multivariate genomic and transcriptomic determinants of imaging-derived personalized therapeutic needs in Parkinson's disease.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Distinct Longitudinal Clinical-Neuroanatomical Trajectories in Parkinson's Disease Clinical Subtypes: Insight toward Precision Medicine.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Beyond the usual suspects: multi-factorial computational models in the search for neurodegenerative disease mechanisms.Translational psychiatry · 2024Review
- In-vivo neuronal dysfunction by Aβ and tau overlaps with brain-wide inflammatory mechanisms in Alzheimer's disease.Frontiers in aging neuroscience · 2024Article
- Patient-specific models link neurotransmitter receptor mechanisms with motor and visuospatial axes of Parkinson's disease.Nature communications · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Due to the marked interpersonal neuropathologic and clinical heterogeneity of Parkinson's disease (PD), current interventions are not personalized and fail to benefit all patients. Furthermore, we continue to lack well-established methods and clinical tests to tailor interventions at the individual level in PD. Here, we identify the genetic determinants of individual-tailored treatment needs derived from longitudinal multimodal neuroimaging data in 294 PD patients (PPMI data). Advanced multivariate statistical analysis revealed that both genomic and blood transcriptomic data significantly explain (P < 0.01, FWE-corrected) the interindividual variability in therapeutic needs associated with dopaminergic, functional, and structural brain reorganization. We confirmed a high overlap between the identified highly predictive molecular pathways and determinants of levodopa clinical responsiveness, including well-known (Wnt signaling, angiogenesis, dopaminergic activity) and recently discovered (immune markers, gonadotropin-releasing hormone receptor) pathways/components. In addition, the observed strong correspondence between the identified genomic and baseline-transcriptomic determinants of treatment needs/response supports the genome's active role at the time of patient evaluation (i.e., beyond individual genetic predispositions at birth). This study paves the way for effectively combining genomic, transcriptomic and neuroimaging data for implementing successful individually tailored interventions in PD and extending our pathogenetic understanding of this multifactorial and heterogeneous disorder.
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