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

Journal of Personalized Medicine

Kun-Hsien Chou¹  Meng-Hsiang Chen²  Chiun-Chieh Yu²  Chia-Yin Lu²  Yueh-Sheng Chen²  Wei-Che Lin²  Cheng-Hsien Lu³  Yi-Yun Lin⁴ 

[1] Brain Research Center, National Yang Ming Chiao Tung University, Taipei 112, Taiwan;Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan;Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan;Philosophy in Nursing, School of Nursing, Shu Zen College of Medicine and Management, Number 452, Hwan-Chio Rd, Luju Dist, Kaohsiung 821, Taiwan;

关键词: cognition;    dementia;    gray matter atrophy;    misfolding protein;    Parkinson’s disease;   

DOI  :  10.3390/jpm11080702

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown