Serum p-tau217 Is a Prognostic Indicator of Cognitive Impairment in Idiopathic REM Sleep Behavior Disorder.

The value of neurofilament light chain (NfL) levels as a biomarker for the diagnosis and differential diagnosis in patients with Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) remains controversial. Furthermore, few studies have directly compared NfL levels among specific APS categories. This study aimed to compare cerebrospinal fluid (CSF) and blood NfL levels among PD, APS, other PD-related disorders, and controls, as well as rank NfL levels across these groups. PubMed, Embase, Web of Science, and the Cochrane Library were searched from the inception up to November 1st, 2024, to identify eligible studies reporting CSF or blood NfL concentrations in PD, PD dementia (PDD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), corticobasal syndrome (CBS), vascular parkinsonism (VP), essential tremor (ET), idiopathic rapid eye movement sleep behavior disorder (iRBD), and controls. The Bayesian approach was utilized to estimate the standardized mean difference (SMD) and the associated 95% credible intervals (CrIs) of NfL levels. The surface under the cumulative ranking curve (SUCRA) was employed to evaluate the ranking probabilities of NfL levels. Subgroup analysis and meta-regression were conducted to explore the sources of heterogeneity. The present network meta-analysis (NMA) included 78 studies with 13,120 participants (4050 controls, 5021 PD, 191 PDD, 1173 MSA, 887 PSP, 1254 DLB, 319 CBS, 160 ET, 65 iRBD, and 0 VP). Of these, the NMA of CSF NfL included 34 studies with 6,013 participants, while the NMA of blood NfL included 49 studies with 7,787 participants. Both CSF and blood NfL levels were significantly elevated in patients with PD and APS compared to controls. Compared to PD patients, CSF NfL levels were significantly elevated in MSA (SMD 1.85; 95% CrI 1.55-2.15), CBS (1.42; 1.08-1.75), PSP (1.35; 1.06-1.64), and DLB 0.52; 0.20-0.85) patients. Similarly, blood NfL levels were significantly higher in patients with MSA (1.36; 1.02-1.71), PDD (1.19; 0.65-1.72), PSP (1.15; 0.77-1.54), CBS (0.92; 0.11-1.72), and DLB (0.63; 0.14-1.12) compared to PD. Among APS, CSF NfL levels in MSA patients were significantly higher than those in PSP, DLB, and CBS patients, while blood NfL levels in MSA patients were significantly higher only compared to DLB. In both CSF and blood NfL, MSA patients exhibited the highest probability of ranking first for NfL level elevations (CSF: SUCRA = 0.998; blood: SUCRA = 0.925). Age significantly influenced the SMD of the comparison between MSA and PD in CSF NfL (β = -0.15; p = 0.016). CSF and blood NfL levels in PD and APS are higher than those in controls, and all APS categories show higher levels than PD, suggesting that NfL levels may serve as a potential biomarker for the differential diagnosis between PD and APS. However, caution is warranted when using NfL as a diagnostic biomarker for PD. Significant differences in NfL levels are also observed between certain APS categories. Patients with MSA exhibit the highest NfL levels among PD and related disorders.

Dissociable contribution of plasma NfL and p-tau181 to cognitive impairment in Parkinson's disease

BackgroundCo‐pathology between Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia with Lewy bodies (DLB) remains poorly understood but is relevant for trial design. We aimed to compare CSF markers of amyloid, tau, and neurodegeneration (ATN) and α‐synuclein between AD, PD, DLB and controls, and investigate the influence of demographical, genetic, and clinical factors on amyloid positivity.MethodAs part of the EPND study, we included 337 individuals with AD, PD, DLB and controls from 6 centers. CSF Aß1‐42, p‐tau181, NfL, and α‐Syn were centrally measured using NeuroToolKit (Roche Diagnostics International Ltd), and clinical data were harmonized. Controls were individuals with normal cognition and normal Aß1‐42. AD was defined as abnormal Aß1‐42 without meeting clinical criteria of DLB or PD. Data were analyzed by general linear models adjusted for age and sex.Result38% individuals were female, and mean age was 67 years. 170 individuals had AD, 74 PD, 66 DLB, and 27 were controls (Table 1). AD individuals showed lower Aß1‐42 levels compared to all other groups (Figure 1). DLB individuals had lower Aß1‐42 levels than those with PD, with both groups displaying lower levels than controls. P‐tau181 concentrations were higher in AD relative to DLB and PD (both p<0.001), with DLB showing higher (p=0.013) and PD lower (p=0.007) levels than controls. Relative to controls, α‐Syn levels were lower in AD, DLB and PD (p=0.016, p=0.016, and p=0.019, respectively). NfL levels were higher in AD (p=0.003) and DLB (p=0.009) compared to controls. 80% of DLB and 58% of PD individuals were amyloid‐positive. Compared to amyloid‐negative ones, amyloid‐positive DLB and PD individuals had lower α‐Syn levels (both p<0.001, Figure 2). Amyloid‐positive PD individuals had lower p‐tau181 levels compared to amyloid‐negative ones (p<0.001). No differences were observed between amyloid‐positive and negative DLB and PD individuals regarding NfL levels. Age, sex, APOE‐ε4, MMSE, and MDS‐UPDRS‐III score were not related to amyloid positivity in DLB and PD.ConclusionAmyloid pathology is highly prevalent in DLB and PD and associated with lower α‐synuclein levels. α‐Synuclein levels are also decreased in AD. This highlights overlapping pathologies in AD, DLB and PD and has significant implications for clinical trial designs.

Association of serum neurofilament light chain and glial fibrillary acidic protein levels with cognitive decline in Parkinson’s disease

This study set out to investigate the relationship between serum neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and various non-motor symptoms (NMSs) in patients with Parkinson's disease (PD). The study included 37 healthy controls (HCs) and 51 PD patients. Clinical assessments of PD symptoms were conducted for all PD patients. The NMSS was utilised to evaluate the NMS burden (NMSB) in individuals. Based on the severity of NMSB, we further categorised the PD group into two subgroups: mild-moderate NMSB group and severe-very severe NMSB group. The amounts of NFL and GFAP in the serum were measured using an extremely sensitive single molecule array (Simoa) method. Statistical analyses were performed on the collected data using SPSS 26.0 and R (version 3.6.3). Serum GFAP and NFL levels in the PD group with severe-very severe NMSB were significantly higher than those in the mild-moderate NMSB group (GFAP: P < 0.007; NFL: P < 0.009). Serum NFL and GFAP levels had positive correlations with NMSS total scores (GFAP: r = 0.326, P = 0.020; NFL: r = 0.318, P = 0.023) and multiple subdomains. The relationship between the attention/memory domains of NMSS and NFL levels is significantly positive (r = 0.283, P = 0.044). Similarly, the mood/apathy domains of NMSS are also significantly positively correlated with GFAP levels (r = 0.441, P = 0.001). Patients with emotional problems or cognitive impairment had higher GFAP or NFL levels, respectively. Furthermore, it has been demonstrated that NMSs play a mediating role in the quality of life of patients with PD. Moreover, the combination of NFL and GFAP has proven to be more effective than using a single component in identifying PD patients with severe-very severe NMSB. The severity of NMSs in PD patients, particularly cognitive and emotional symptoms, was found to be associated with the levels of serum NFL and GFAP. This study marks the first attempt to examine the connection between NMSs of PD and the simultaneous identification of NFL and GFAP levels.

BackgroundWhile evidence suggests complement system involvement in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease (PD), its association with disease biomarkers remains unclear. We investigated the relationship of complement factors with amyloid, tau, NfL, and α‐synuclein in CSF in AD, DLB, PD, and controls.MethodWe included 321 individuals with AD, DLB, PD, and controls from 6 centers of the EPND study. CSF Aβ42/40, p‐tau181, NfL, and α‐syn were centrally measured using NeuroToolKit (Roche Diagnostics), and 14 CSF complement factors using Milliplex (Merck KGaA). Controls were defined as normal cognition and normal Aβ42/40, whereas AD as abnormal Aβ42/40 without meeting clinical criteria of DLB or PD. Linear regression models adjusted for age and sex were used. Associations were post‐hoc compared between individuals with low(≤23), intermediate(24‐27), and high(≥28) MMSE scores.ResultSample characteristics are presented in Table 1. Lower Aβ42/40 levels were associated with lower levels of 7 complement factors in controls and with higher C1q and C2 levels specifically in AD (Figure 1, Figure 2). No associations of Aβ42/40 with complement were found in DLB and PD. Higher p‐tau181 levels were associated with increased levels of 7 complement factors in controls and 6 in AD, and showed fewer associations in DLB and PD. The strength of p‐tau181 associations with complement was similar across groups. Higher NfL levels were widely associated with higher complement factor levels in controls (13) and AD (12), and less in PD (6) and DLB (4). Higher α‐syn levels were broadly associated with higher complement factor levels in AD (13), controls (12), and DLB (12), but only minimally in PD (1). The strength of these NfL and α‐syn associations with complement was not disease‐specific. Conversely, compared to all groups, in PD higher α‐syn levels were associated with lower C5, C5a, C9, factor‐I and properdin levels. Individuals with intermediate MMSE scores largely drove the associations of α‐syn with complement in AD. MMSE level did not clearly impact other associations.ConclusionCSF complement factors were associated with amyloid, tau, NfL, and α‐synuclein, suggesting complement system involvement in several neurodegenerative diseases. Complement showed disease‐specific associations with amyloid in AD and α‐synuclein in PD.

Clinical diagnosis of multiple system atrophy is challenging and many patients with Lewy body disease (i.e. Parkinson's disease or dementia with Lewy bodies) or progressive supranuclear palsy are misdiagnosed as having multiple system atrophy in life. The clinical records of 203 patients with a clinical diagnosis of multiple system atrophy were reviewed to identify diagnostic pitfalls. We also examined 12 features supporting a diagnosis of multiple system atrophy (red flag features: orofacial dystonia, disproportionate antecollis, camptocormia and/or Pisa syndrome, contractures of hands or feet, inspiratory sighs, severe dysphonia, severe dysarthria, snoring, cold hands and feet, pathological laughter and crying, jerky myoclonic postural/action tremor and polyminimyoclonus) and seven disability milestones (frequent falls, use of urinary catheters, wheelchair dependent, unintelligible speech, cognitive impairment, severe dysphagia, residential care). Of 203 cases, 160 (78.8%) were correctly diagnosed in life and had pathologically confirmed multiple system atrophy. The remaining 21.2% (43/203) had alternative pathological diagnoses including Lewy body disease (12.8%; n = 26), progressive supranuclear palsy (6.4%; n = 13), cerebrovascular diseases (1%; n = 2), amyotrophic lateral sclerosis (0.5%; n = 1) and cerebellar degeneration (0.5%; n = 1). More patients with multiple system atrophy developed ataxia, stridor, dysphagia and falls than patients with Lewy body disease; resting tremor, pill-rolling tremor and hallucinations were more frequent in Lewy body disease. Although patients with multiple system atrophy and progressive supranuclear palsy shared several symptoms and signs, ataxia and stridor were more common in multiple system atrophy. Multiple logistic regression analysis revealed increased likelihood of multiple system atrophy versus Lewy body disease and progressive supranuclear palsy if a patient developed orthostatic hypotension or urinary incontinence with the requirement for urinary catheters [multiple system atrophy versus Lewy body disease: odds ratio (OR): 2.0, 95% confidence interval (CI): 1.1-3.7, P = 0.021; multiple system atrophy versus progressive supranuclear palsy: OR: 11.2, 95% CI: 3.2-39.2, P < 0.01]. Furthermore, autonomic dysfunction within the first 3 years from onset can differentiate multiple system atrophy from progressive supranuclear palsy (multiple system atrophy versus progressive supranuclear palsy: OR: 3.4, 95% CI: 1.2-9.7, P = 0.023). Multiple system atrophy patients with predominant parkinsonian signs had a higher number of red flag features than patients with Lewy body disease (OR: 8.8, 95% CI: 3.2-24.2, P < 0.01) and progressive supranuclear palsy (OR: 4.8, 95% CI: 1.7-13.6, P < 0.01). The number of red flag features in multiple system atrophy with predominant cerebellar signs was also higher than in Lewy body disease (OR: 7.0, 95% CI: 2.5-19.5, P < 0.01) and progressive supranuclear palsy (OR: 3.1, 95% CI: 1.1-8.9, P = 0.032). Patients with multiple system atrophy had shorter latency to reach use of urinary catheter and longer latency to residential care than progressive supranuclear palsy patients, whereas patients with Lewy body disease took longer to reach multiple milestones than patients with multiple system atrophy. The present study has highlighted features which should improve the ante-mortem diagnostic accuracy of multiple system atrophy.

Parkinson disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB) share alpha-synuclein immunoreactivity. These "synucleinopathies" have overlapping signs and symptoms, but less is known about similarities and differences in their cognitive and neuropsychiatric profiles. We compared the cognitive and neuropsychiatric profiles of individuals with PD, MSA, and DLB. Overall, the DLB group showed the most cognitive impairment, the MSA group demonstrated milder impairment, and the PD group was the least cognitively impaired. The DLB and MSA groups showed worse executive function and visuospatial skills than PD, whereas DLB showed impaired memory relative to both PD and MSA. On the neuropsychiatric screening, all groups endorsed depression and anxiety; the DLB group alone endorsed delusions and disinhibition. Consistent with their greater level of cognitive and neuropsychiatric impairment, the DLB group showed the greatest amount of functional impairment on a measure of instrumental activities of daily living (Functional Activities Questionnaire). We found that MSA subjects had cognitive difficulties that fell between the mild deficits of the PD group and the more severe deficits of the DLB group. PD, MSA, and DLB groups have similar neuropsychiatric profiles of increased depression and anxiety. Similar underlying alpha-synuclein pathology may contribute to these shared features.

Neurofilament light chain (NfL) has recently emerged as a key indicator of neurodegeneration. In this study, our hypothesis is that the levels of blood-derived NfL and its accumulation during the Parkinson's disease (PD) progression could serve as a potential biomarker for predicting subsequent cognitive decline. To investigate this, we conducted a study utilizing a large single-center cohort. The study included 193 participants, consisting of 106 cognitively normal PD (PD-CN) patients and 87 normal controls (NC) individuals. Serum NfL concentrations were measured. PD patients were followed up for clinical assessment at an average of 2 ± 0.6 years. The serum NfL levels were significantly higher in PD-CN patients compared to NC. PD-CN patients and NC at follow-up time exhibited higher serum NfL levels compared to those at baseline. PD patients with high serum NfL levels were found to have a higher likelihood of transitioning from normal cognition to mild cognitive impairment (MCI) or dementia (Hazard ratio (HR) 1.107, 95% confidence intervals (CI) 1.010-1.213, p = 0.030). The area under the curve (AUC) for PD-CN conversion to MCI or dementia at follow-up time was determined to be 0.684 (95% CI 0.569-0.799). In conclusion, our study found that PD patients have significantly higher levels of serum NfL compared to individuals without PD. Furthermore, serum NfL levels increase as PD progresses and can predict cognitive impairment within a 2-year timeframe. Serum NfL may serve as a feasible, non-invasive biomarker of cognitive progression in PD. However, further studies and functional experiments are needed to validate these findings.

In "Blood NfL: a biomarker for disease severity and progression in Parkinson disease," Lin et al. reported that neurofilament light chain (NfL) levels are significantly higher in patients with multiple system atrophy (MSA) than patients with Parkinson disease (PD) or healthy controls and that, for patients with PD, NfL levels increase with disease severity. Van Rumund et al. agreed that NfL could distinguish PD from MSA but questioned the finding that NfL increases with disease severity in patients with PD because (1) they previously found that NfL levels in patients with PD to be similar to controls, (2) the determination of NfL cutoff values and the assessment for the relationship between PD disease progression and blood NfL were performed in the same population, and (3) the definitions used to define motor and cognitive decline may be overly sensitive. However, Van Rumun et al. and Lin and Chiu both suggested that the differences in their NfL level findings in patients with PD may be explained by a greater number of patients with advanced PD in the study of Lin et al. Although NfL may be a useful biomarker to distinguish MSA from PD, further research is needed on the role of NfL as a marker of PD disease progression. In "Blood NfL: a biomarker for disease severity and progression in Parkinson disease," Lin et al. reported that neurofilament light chain (NfL) levels are significantly higher in patients with multiple system atrophy (MSA) than patients with Parkinson disease (PD) or healthy controls and that, for patients with PD, NfL levels increase with disease severity. Van Rumund et al. agreed that NfL could distinguish PD from MSA but questioned the finding that NfL increases with disease severity in patients with PD because (1) they previously found that NfL levels in patients with PD to be similar to controls, (2) the determination of NfL cutoff values and the assessment for the relationship between PD disease progression and blood NfL were performed in the same population, and (3) the definitions used to define motor and cognitive decline may be overly sensitive. However, Van Rumun et al. and Lin and Chiu both suggested that the differences in their NfL level findings in patients with PD may be explained by a greater number of patients with advanced PD in the study of Lin et al. Although NfL may be a useful biomarker to distinguish MSA from PD, further research is needed on the role of NfL as a marker of PD disease progression.

Epilepsy treatment aims not only to control seizures but also to enhance quality of life. However, reliable blood-based biomarkers for epilepsy-related cognitive impairment are lacking. This study investigated the association between plasma neurofilament light chain (NfL) levels and cognitive function in epilepsy by integrating evidence from observational and Mendelian randomization (MR) analyses across different populations. We conducted a cross-sectional observational study at the First Hospital of Jilin University, enrolling 152 adults with epilepsy. Demographic and clinical information was collected, and cognitive status and psychological status were assessed using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Memory and Executive Screening (MES) scale, Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). Plasma NfL levels were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses included logistic regression, linear regression, and receiver-operating characteristic (ROC) curve analysis. In parallel, two-sample MR was performed using genome-wide association study (GWAS) summary statistics from European cohorts. Shared genetic variants between epilepsy and cognitive impairment were identified using multi-trait analysis of GWAS (MTAG) and cross-phenotype association (CPASSOC), and served as instrumental variables to estimate the causal effect on plasma NfL levels. Plasma NfL levels were significantly higher in the cognitively impaired group. After adjusting for confounders, elevated NfL levels remained independently associated with increased risk of cognitive impairment and inversely correlated with cognitive scores. ROC curve analysis showed high diagnostic accuracy of plasma NfL. MR analysis confirmed a positive causal relationship between epilepsy-related cognitive impairment and plasma NfL levels. Plasma NfL is associated with cognitive impairment in epilepsy and may serve as an early blood-based biomarker for identifying cognitive dysfunction in this population.

To examine whether plasma neurofilament light chain (NfL) levels were associated with motor and cognitive progression in Parkinson disease (PD). This prospective follow-up study enrolled 178 participants, including 116 with PD, 22 with multiple system atrophy (MSA), and 40 healthy controls. We measured plasma NfL levels with electrochemiluminescence immunoassay. Patients with PD received evaluations of motor and cognition at baseline and at a mean follow-up interval of 3 years. Changes in the Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score and Mini-Mental State Examination score were used to assess motor and cognition progression. Plasma NfL levels were significantly higher in the MSA group than in the PD and healthy groups (35.8 ± 6.2, 17.6 ± 2.8, and 10.6 ± 2.3 pg/mL, respectively, p < 0.001). In the PD group, NfL levels were significantly elevated in patients with advanced Hoehn-Yahr stage and patients with dementia (p < 0.001). NfL levels were modestly correlated with UPDRS part III scores (r = 0.42, 95% confidence interval 0.46-0.56, p < 0.001). After a mean follow-up of 3.4 ± 1.2 years, a Cox regression analysis adjusted for age, sex, disease duration, and baseline motor or cognitive status showed that higher baseline NfL levels were associated with higher risks for either motor or cognition progression (p = 0.029 and p = 0.015, respectively). Plasma NfL levels correlated with disease severity and progression in terms of both motor and cognitive functions in PD. This study provides Class III evidence that plasma NfL level distinguishes PD from MSA and is a surrogate biomarker for PD progression.

Our objective was to examine whether rapid eye movement (REM) sleep behavior disorder occurs in disproportionally greater frequency in multiple system atrophy (MSA), Parkinson's disease (PD), and dementia with Lewy bodies (DLB), collectively known as the synucleinopathies, compared to other nonsynucleinopathy neurodegenerative disorders. In study 1, we reviewed the clinical records of 398 consecutive patients evaluated at Mayo Clinic Rochester for parkinsonism and/or cognitive impairment. The frequency of suspected and polysomnogram (PSG)-confirmed REM sleep behavior disorder (RBD) among subjects with the synucleinopathies MSA, PD, or DLB was compared to the frequency among subjects with the nonsynucleinopathies Alzheimer's disease (AD), frontotemporal dementia (FTD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), mild cognitive impairment (MCI), primary progressive aphasia (PPA), and posterior cortical atrophy (PCA). In study 2, we reviewed the clinical records of 360 consecutive patients evaluated at Mayo Clinic Jacksonville for parkinsonism and/or cognitive impairment. The frequency of probable RBD among patients with PD and DLB was compared to the frequency among patients with AD and MCI. In study 3, we reviewed the brain biopsy or postmortem autopsy diagnoses of 23 Mayo Clinic Rochester patients who had been clinically examined for possible RBD and a neurodegenerative disorder. In study 1, patients with MSA, PD, or DLB were more likely to have probable and PSG-confirmed RBD compared to subjects with the nonsynucleinopathies (probable RBD 77/120=64% vs. 7/278=3%, p < 0.01; PSG-confirmed RBD 47/120=39% vs. 1/278=0%, p < 0.01). In study 2, patients with PD and DLB were more likely to have probable RBD compared to those with AD and MCI (56% vs. 2%, p < 0.01). In study 3, of the 23 autopsied patients who had been questioned about possible RBD, 10 were clinically diagnosed with RBD. The neuropathologic diagnoses in these 10 included Lewy body disease in nine, and MSA in one. Of the other 13 cases, 12 did not have a history suggesting RBD, and the one case who did had normal electromyographic atonia during REM sleep on PSG and autopsy findings of PSP. Only one of these 13 had a synucleinopathy. The positive predictive values for RBD indicating a synucleinopathy for studies 1-3 were 91.7%, 94.3%, and 100.0%, respectively. Clinically suspected and PSG-proven RBD occurs with disproportionally greater frequency in MSA, PD, and DLB compared to other neurodegenerative disorders. In the setting of degenerative dementia and/or parkinsonism, we hypothesize that RBD is a manifestation of an evolving synucleinopathy.

Mild cognitive impairment is one of the non-motor symptoms in Parkinson's disease (PD) and multiple system atrophy (MSA). Few studies have previously been conducted on the correlation between serum uric acid (SUA) and lipid levels and mild cognitive impairment in PD and MSA. Participants included 149 patients with PD and 99 patients with MSA. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function. Evaluations were conducted on SUA and lipid levels, which included triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC). Patients with PD and MSA diagnosed with mild cognitive impairment demonstrated multiple cognitive domain impairment when compared with patients with normal cognition. Attentional impairment was more pronounced in patients with MSA when compared with PD (p = 0.001). In PD, the risk of mild cognitive impairment was lower in the highest quartiles and secondary quartile of SUA than in the lowest quartiles (odds ratio [OR] = 0.281, 95% confidence intervals [CI]: 0.097-0.810, p = 0.019; and OR = 0.317, 95% CI: 0.110-0.911, p = 0.033). In MSA, the risk of mild cognitive impairment was lower in the third and highest quartile of SUA than in the lowest quartile (OR = 0.233, 95% CI: 0.063-0.868, p = 0.030; and OR = 0.218, 95% CI: 0.058-0.816, p = 0.024). In patients with PD, the MoCA scores were negatively correlated with TC levels (r = -0.226, p = 0.006) and positively correlated with SUA levels (r = 0.206, p = 0.012). In MSA, the MoCA scores were positively correlated with SUA levels (r = 0.353, p = 0.001). Lower SUA levels and higher TC levels are a possible risk factor for the risk and severity of mild cognitive impairment in PD. Lower SUA levels are a possible risk factor for the risk and severity of mild cognitive impairment in MSA.

Convergence of Heat Shock Protein 90 with Ubiquitin in Filamentous α-Synuclein Inclusions of α-Synucleinopathies