Dataset Information

Brain Atrophy Mediates the Relationship between Misfolded Proteins Deposition and Cognitive Impairment in Parkinson's Disease.

ABSTRACT: Parkinson's disease is associated with cognitive decline, misfolded protein deposition and brain atrophy. We herein hypothesized that structural abnormalities may be mediators between plasma misfolded proteins and cognitive functions. Neuropsychological assessments including five domains (attention, executive, speech and language, memory and visuospatial functions), ultra-sensitive immunomagnetic reduction-based immunoassay (IMR) measured misfolded protein levels (phosphorylated-Tau, Amyloidβ-42 and 40, α-synuclein and neurofilament light chain) and auto-segmented brain volumetry using FreeSurfur were performed for 54 Parkinson's disease (PD) patients and 37 normal participants. Our results revealed that PD patients have higher plasma misfolded protein levels. Phosphorylated-Tau (p-Tau) and Amyloidβ-42 (Aβ-42) were correlated with atrophy of bilateral cerebellum, right caudate nucleus, and right accumbens area (RAA). In mediation analysis, RAA atrophy completely mediated the relationship between p-Tau and digit symbol coding (DSC). RAA and bilateral cerebellar cortex atrophy partially mediated the Aβ-42 and executive function (DSC and abstract thinking) relationship. Our study concluded that, in PD, p-Tau deposition adversely impacts DSC by causing RAA atrophy. Aβ-42 deposition adversely impacts executive functions by causing RAA and bilateral cerebellum atrophy.

SUBMITTER: Yu CC

PROVIDER: S-EPMC8401428 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Brain Atrophy Mediates the Relationship between Misfolded Proteins Deposition and Cognitive Impairment in Parkinson's Disease.

Yu Chiun-Chieh CC Lu Chia-Yin CY Chen Meng-Hsiang MH Chen Yueh-Sheng YS Lu Cheng-Hsien CH Lin Yi-Yun YY Chou Kun-Hsien KH Lin Wei-Che WC

Journal of personalized medicine 20210723 8

Parkinson's disease is associated with cognitive decline, misfolded protein deposition and brain atrophy. We herein hypothesized that structural abnormalities may be mediators between plasma misfolded proteins and cognitive functions. Neuropsychological assessments including five domains (attention, executive, speech and language, memory and visuospatial functions), ultra-sensitive immunomagnetic reduction-based immunoassay (IMR) measured misfolded protein levels (phosphorylated-Tau, Amyloidβ-42 ...[more]

PMID: 34442345

Similar Datasets

Project description:Background: Neuritic plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer's disease (AD), while the role of brain amyloid deposition in the clinical manifestation or brain atrophy remains unresolved. We aimed to explore the relation between brain amyloid deposition, cortical thickness, and plasma biomarkers. Methods: We used 11C-Pittsburgh compound B-positron emission tomography to assay brain amyloid deposition, magnetic resonance imaging to estimate cortical thickness, and an immunomagnetic reduction assay to measure plasma biomarkers. We recruited 39 controls, 25 subjects with amnesic mild cognitive impairment (aMCI), and 16 subjects with AD. PiB positivity (PiB+) was defined by the upper limit of the 95% confidence interval of the mean cortical SUVR from six predefined regions (1.0511 in this study). Results: All plasma biomarkers showed significant between-group differences. The plasma Aβ40 level was positively correlated with the mean cortical thickness of both the PiB+ and PiB- subjects. The plasma Aβ40 level of the subjects who were PiB+ was negatively correlated with brain amyloid deposition. In addition, the plasma tau level was negatively correlated with cortical thickness in both the PiB+ and PiB- subjects. Moreover, cortical thickness was negatively correlated with brain amyloid deposition in the PiB+ subjects. In addition, the cut-off point of plasma tau for differentiating between controls and AD was higher in the PiB- group than in the PiB+ group (37.5 versus 25.6 pg/ml, respectively). Lastly, ApoE4 increased the PiB+ rate in the aMCI and control groups. Conclusion: The contributions of brain amyloid deposition to cortical atrophy are spatially distinct. Plasma Aβ40 might be a protective indicator of less brain amyloid deposition and cortical atrophy. It takes more tau pathology to reach the same level of cognitive decline in subjects without brain amyloid deposition, and ApoE4 plays an early role in amyloid pathogenesis.

Dataset Information

Brain Atrophy Mediates the Relationship between Misfolded Proteins Deposition and Cognitive Impairment in Parkinson's Disease.

Publications

Brain Atrophy Mediates the Relationship between Misfolded Proteins Deposition and Cognitive Impairment in Parkinson's Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets