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Principal Component Analysis versus Subject's Residual Profile Analysis for Neuroinflammation Investigation in Parkinson Patients: A PET Brain Imaging Study.

ABSTRACT: Dysfunction of neurons in the central nervous system is the primary pathological feature of Parkinson's disease (PD). Despite different triggering, emerging evidence indicates that neuroinflammation revealed through microglia activation is critical for PD. Moreover, recent investigations sought a potential relationship between Lrrk2 genetic mutation and microglia activation. In this paper, neuroinflammation in sporadic PD, Lrrk2-PD and unaffected Lrrk2 mutation carriers were investigated. The principal component analysis (PCA) and the subject's residual profile (SRP) techniques were performed on multiple groups and regions of interest in 22 brain-regions. The 11C-PBR28 binding profiles were compared in four genotypes depending on groups, i.e., HC, sPD, Lrrk2-PD and UC, using the PCA and SPR scores. The genotype effect was found as a principal feature of group-dependent 11C-PBR28 binding, and preliminary evidence of a MAB-Lrrk2 mutation interaction in manifest Parkinson's and subjects at risk was found.

SUBMITTER: Mabrouk R

PROVIDER: S-EPMC8954189 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Principal Component Analysis versus Subject's Residual Profile Analysis for Neuroinflammation Investigation in Parkinson Patients: A PET Brain Imaging Study.

Mabrouk Rostom R

Journal of imaging 20220225 3

Dysfunction of neurons in the central nervous system is the primary pathological feature of Parkinson's disease (PD). Despite different triggering, emerging evidence indicates that neuroinflammation revealed through microglia activation is critical for PD. Moreover, recent investigations sought a potential relationship between Lrrk2 genetic mutation and microglia activation. In this paper, neuroinflammation in sporadic PD, Lrrk2-PD and unaffected Lrrk2 mutation carriers were investigated. The pr ...[more]

PMID: 35324611

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Project description:Voxel-based principal-component analysis allows for an identification of patterns of glucose metabolism and amyloid deposition related to the conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD). The present study aimed to validate these AD conversion-related patterns (ADCRPs) against neuropathologic findings. Methods: We included patients from the Alzheimer's Disease Neuroimaging Initiative who underwent autopsy and for whom 18F-FDG PET (30 AD, 6 MCI, 2 cognitively normal) and amyloid-β (Aβ) PET (17 AD, 3 MCI, 2 cognitively normal) were available. Pattern expression scores (PESs) of the 18F-FDG- and Aβ-ADCRP were compared with Braak tangle stage and Thal amyloid phase, respectively. Mean 18F-FDG uptake and mean 18F-AV-45 SUV ratio (SUVr) in regions of hypometabolism and elevated amyloid load typical of AD, respectively, were used as volume-of-interest-based PET measures. The diagnostic performance for identifying none-to-low vs. intermediate-to-high AD neuropathologic change (ADNC) was assessed for all biomarkers. Results: We observed significant associations between PES of 18F-FDG-ADCRP and Braak stage (ρ > 0.48, P < 0.005) and between PES of Aβ-ADCRP and Thal phase (ρ > 0.66, P < 0.001). PES of 18F-FDG-ADCRP, PES of Aβ-ADCRP, and their combination identified intermediate-to-high ADNC with an area under the receiver-operating-characteristic curve (AUC) of 0.80, 0.95, and 0.98 (n = 22), respectively. Mean 18F-FDG uptake and mean 18F-AV-45 SUVr in AD-typical regions were also significantly associated with Braak stage (|ρ| > 0.45, P < 0.01) and Thal phase (ρ > 0.55, P < 0.01), respectively. Volume-of-interest-based PET measures discriminated between ADNC stages with an AUC of 0.79, 0.88, and 0.90 for mean 18F-FDG uptake, mean 18F-AV-45 SUVr, and their combination (n = 22), respectively. Contemplating all subjects with available 18F-FDG PET and neuropathology information (n = 38), PES of 18F-FDG-ADCRP was a significant predictor of intermediate-to-high ADNC (AUC = 0.72), whereas mean 18F-FDG uptake was not (AUC = 0.66), although the difference between methods was not significant. Conclusion: PES of 18F-FDG-ADCRP, a measure of neurodegeneration, shows close correspondence with the extent of tau pathology, as assessed by Braak tangle stage. PES of Aβ-ADCRP is a valid biomarker of underlying amyloid pathology, as demonstrated by its strong correlation with Thal phase. The combination of ADCRPs performed better than 18F-FDG-ADCRP alone, although there was only negligible improvement compared with Aβ-ADCRP.

Dataset Information

Principal Component Analysis versus Subject's Residual Profile Analysis for Neuroinflammation Investigation in Parkinson Patients: A PET Brain Imaging Study.

Publications

Principal Component Analysis versus Subject's Residual Profile Analysis for Neuroinflammation Investigation in Parkinson Patients: A PET Brain Imaging Study.

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