The Association of CSF sTREM2 With Cognitive Decline and Its Dynamic Change in Parkinson's Disease: Analysis of the PPMI Cohort

Qin, Qixiong; Wan, Hengming; Wang, Danlei; Li, Jingyi; Qu, Yi; Zhao, J. W.; Li, Jiangting; Xue, Zhenyi

doi:10.3389/fnagi.2022.892493

Cited by 16 publications

(11 citation statements)

References 60 publications

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“…An increase in cerebrospinal fluid (CSF) alpha-synuclein (α-syn) was association with further deterioration of motor and cognitive deficits ( Hall et al, 2015 ; Majbour et al, 2016 ). CSF soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) may be a promising predictor for the cognitive decline in PD rather than a diagnostic biomarker ( Qin et al, 2022 ). CSF GCase activity has been shown to be significantly reduced in PD compared to controls ( Paciotti et al, 2019 ; Parnetti et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Neurofilament light as a biomarker for motor decline in Parkinson’s disease

Liu

Dou

et al. 2022

Front. Neurosci.

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ObjectivesThe aim of this study was to determine whether neurofifilament light (NfL) could reflect motor decline and compare the predictive values of cerebrospinal fluid (CSF) and serum NfL in individuals with PD.MethodsCSF/serum samples were collected from patients with PD and healthy controls (HCs) with motor assessments at baseline and after three years of follow-up from the Parkinson’s Progression Markers Initiative (PPMI). Multiple linear regression models and linear mixed-effects models were used to investigate the associations of motor assessments with baseline and longitudinal CSF/serum NfL. Associations between the change rates of motor assessments and CSF/serum NfL were further investigated via multiple linear regression models. Mediating effect analysis was used to research whether CSF alpha-synuclein (α-syn) acts as the mediator between NfL and motor assessments.ResultsWe found patients with PD had higher baseline CSF/serum NfL levels than HCs. Both baseline CSF/serum NfLs and their change rates predicted measurable motor decline in PD assessed by different motor scores. Baseline serum NfL and its rate of change were strongly associated with CSF NfL levels in patients with PD (P < 0.001). Besides, there were also significant differences in CSF/serum NfL levels and predicted values of motor decline between men and women with PD. Mediating effect analysis showed CSF α-syn mediated the effect of CSF NfL on total Unified Parkinson’s Disease Rating Scale (UPDRS) scores and UPDRSIII with 30.6 and 20.2% mediation, respectively.ConclusionOur results indicated that NfL, especially serum NfL concentration, could serve as an easily accessible biomarker to monitor the severity and progression of motor decline in individuals with PD, especially in men with PD. Besides, CSF α-syn acts as a mediator between NfL and motor progression.

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Section: Introductionmentioning

confidence: 99%

Neurofilament light as a biomarker for motor decline in Parkinson’s disease

Liu

Dou

et al. 2022

Front. Neurosci.

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“…Although this result is partially supported by Bartl's study [ 16 ], the exact mechanism remains unclear and further studies are, therefore, required. Furthermore, to our knowledge, Qin et al reached similar results in their analysis of the PPMI cohort: there was also a significant positive correlation between the soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2, a biomarker of microglial activation) and Aβ42 in CSF, both cross-sectionally and longitudinally [ 48 ]. In addition, through a subgroup analysis, our investigation revealed that the intensity of the correlation existing between baseline CSF GFAP and longitudinal CSF T-tau, P-tau, α-syn changes was influenced by Aβ status.…”

Section: Discussionmentioning

confidence: 68%

Cerebrospinal fluid GFAP is a predictive biomarker for conversion to dementia and Alzheimer’s disease-associated biomarkers alterations among de novo Parkinson’s disease patients: a prospective cohort study

Liu

Zuo

et al. 2023

J Neuroinflammation

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Background Dementia is a prevalent non-motor manifestation among individuals with advanced Parkinson’s disease (PD). Glial fibrillary acidic protein (GFAP) is an inflammatory marker derived from astrocytes. Research has demonstrated the potential of plasma GFAP to forecast the progression to dementia in PD patients with mild cognitive impairment (PD–MCI). However, the predictive role of cerebrospinal fluid (CSF) GFAP on future cognitive transformation and alterations in Alzheimer’s disease (AD)-associated CSF biomarkers in newly diagnosed PD patients has not been investigated. Methods 210 de novo PD patients from the Parkinson’s Progression Markers Initiative were recruited. Cognitive progression in PD participants was evaluated using Cox regression. Cross-sectional and longitudinal associations between baseline CSF GFAP and cognitive function and AD-related CSF biomarkers were evaluated using multiple linear regression and generalized linear mixed model. Results At baseline, the mean age of PD participants was 60.85 ± 9.78 years, including 142 patients with normal cognition (PD–NC) and 68 PD–MCI patients. The average follow-up time was 6.42 ± 1.69 years. A positive correlation was observed between baseline CSF GFAP and age (β = 0.918, p < 0.001). There was no statistically significant difference in baseline CSF GFAP levels between PD–NC and PD–MCI groups. Higher baseline CSF GFAP predicted greater global cognitive decline over time in early PD patients (Montreal Cognitive Assessment, β = − 0.013, p = 0.014). Furthermore, Cox regression showed that high baseline CSF GFAP levels were associated with a high risk of developing dementia over an 8-year period in the PD–NC group (adjusted HR = 3.070, 95% CI 1.119–8.418, p = 0.029). In addition, the baseline CSF GFAP was positively correlated with the longitudinal changes of not only CSF α-synuclein (β = 0.313, p < 0.001), but also CSF biomarkers associated with AD, namely, amyloid-β 42 (β = 0.147, p = 0.034), total tau (β = 0.337, p < 0.001) and phosphorylated tau (β = 0.408, p < 0.001). Conclusions CSF GFAP may be a valuable prognostic tool that can predict the severity and progression of cognitive deterioration, accompanied with longitudinal changes in AD-associated pathological markers in early PD.

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“…In our series, increased baseline levels of sTREM2 were observed in PD-MCI patients showing cognitive worsening after two years. Accordingly, different investigations from the PPMI cohort reported that CSF sTREM2 has a role in predicting cognitive decline in PD 26 , 52 , being also increased in those patients with positive CSF tau signature 51 – 53 . All these findings, taken together, seem to suggest that CSF sTREM2 may be a promising predictor of worse cognitive outcome rather than a diagnostic biomarker in PD-MCI.…”

Section: Discussionmentioning

confidence: 99%

CSF neurochemical profile and cognitive changes in Parkinson’s disease with mild cognitive impairment

Paoletti

Gaetani

Bellomo

et al. 2023

npj Parkinsons Dis.

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Pathophysiological substrate(s) and progression of Parkinson’s disease (PD) with mild cognitive impairment (PD-MCI) are still matter of debate. Baseline cerebrospinal fluid (CSF) neurochemical profile and cognitive changes after 2 years were investigated in a retrospective series of PD-MCI (n = 48), cognitively normal PD (PD-CN, n = 40), prodromal Alzheimer’s disease (MCI-AD, n = 25) and cognitively healthy individuals with other neurological diseases (OND, n = 44). CSF biomarkers reflecting amyloidosis (Aβ42/40 ratio, sAPPα, sAPPβ), tauopathy (p-tau), neurodegeneration (t-tau, NfL, p-NfH), synaptic damage (α-syn, neurogranin) and glial activation (sTREM2, YKL-40) were measured. The great majority (88%) of PD-MCI patients was A-/T-/N-. Among all biomarkers considered, only NfL/p-NfH ratio was significantly higher in PD-MCI vs. PD-CN (p = 0.02). After 2 years, one-third of PD-MCI patients worsened; such worsening was associated with higher baseline levels of NfL, p-tau, and sTREM2. PD-MCI is a heterogeneous entity requiring further investigations on larger, longitudinal cohorts with neuropathological verification.

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The Association of CSF sTREM2 With Cognitive Decline and Its Dynamic Change in Parkinson's Disease: Analysis of the PPMI Cohort

Cited by 16 publications

References 60 publications

Neurofilament light as a biomarker for motor decline in Parkinson’s disease

Neurofilament light as a biomarker for motor decline in Parkinson’s disease

Cerebrospinal fluid GFAP is a predictive biomarker for conversion to dementia and Alzheimer’s disease-associated biomarkers alterations among de novo Parkinson’s disease patients: a prospective cohort study

CSF neurochemical profile and cognitive changes in Parkinson’s disease with mild cognitive impairment

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