Sex hormones differentially contribute to Parkinson disease in males: A multimodal biomarker study.

BACKGROUND AND PURPOSE: Parkinson disease (PD) presents relevant sex-related differences in epidemiology, pathophysiology, and clinical features, with males being more vulnerable to the disease. Sex hormones might have a role, as the experimental models suggest; however, human-based evidence is scarce. Here, we integrated multimodal biomarkers to investigate the relationships between circulating sex hormones and clinical-pathological features in male PD patients. METHODS: A cohort of 63 male PD patients underwent comprehensive clinical evaluation of motor and nonmotor disturbances; measurement of estradiol, testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) blood levels; and cerebrospinal fluid (CSF) assay of total α-synuclein, amyloid-ß-42, amyloid-ß-40, total tau, and phosphorylated-181 tau levels. A subgroup of 47 PD patients underwent brain volumetry by 3-T magnetic resonance imaging for further correlations. A control group of 56 age-matched individuals was enrolled for comparative analyses. RESULTS: Male PD patients had higher estradiol and testosterone levels than controls. Estradiol had independent inverse associations with Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part 3 score and disease duration; it was also lower in nonfluctuating patients. Testosterone had inverse independent correlations with CSF α-synuclein and right globus pallidus volume. FSH and LH had age-dependent correlations with cognitive impairment and CSF amyloid-ß-42/amyloid-ß-40 ratio. CONCLUSIONS: The study suggested that sex hormones could differentially contribute to clinical-pathological features of PD in male patients. Whereas estradiol might have a protective role in motor impairment, testosterone might be involved in male vulnerability to PD neuropathology. Gonadotropins instead might mediate age-dependent phenomena of amyloidopathy and cognitive decline.

Blood-Brain Barrier Dysfunction and Aß42/40 Ratio Dose-Dependent Modulation with the ApoE Genotype within the ATN Framework.

The definition of Alzheimer's disease (AD) now considers the presence of the markers of amyloid (A), tau deposition (T), and neurodegeneration (N) essential for diagnosis. AD patients have been reported to have increased blood-brain barrier (BBB) dysfunction, but that has not been tested within the ATN framework so far. As the field is moving towards the use of blood-based biomarkers, the relationship between BBB disruption and AD-specific biomarkers requires considerable attention. Moreover, other factors have been previously implicated in modulating BBB permeability, including age, gender, and ApoE status. A total of 172 cognitively impaired individuals underwent cerebrospinal fluid (CSF) analysis for AD biomarkers, and data on BBB dysfunction, demographics, and ApoE status were collected. Our data showed that there was no difference in BBB dysfunction across different ATN subtypes, and that BBB damage was not correlated with cognitive impairment. However, patients with BBB disruption, if measured with a high Qalb, had low Aß40 levels. ApoE status did not affect BBB function but had a dose-dependent effect on the Aß42/40 ratio. These results might highlight the importance of understanding dynamic changes across the BBB in future studies in patients with AD.

Effects of head trauma and sport participation in young-onset Parkinson's disease.

Head trauma (HT) is emerging as an event anticipating onset of neurodegenerative disorders. However, the potential contribution of HT in young-onset cases (YOPD, age at onset < 50) of Parkinson's disease (PD) has not been examined yet. Here, we systematically assessed HT history in PD patients to estimate the risk associated, especially in terms of age of onset, and define the correlations with the clinical-biochemical profile. The Brain Injury Screening Questionnaire (BISQ) was administered to 94 PD patients (31 with YOPD, known monogenic forms excluded) and 70 controls. HT history was correlated with motor and non-motor scores in all patients, and to CSF biomarkers of neurodegeneration (α-synuclein, amyloid-ß42, total and phosporiled-181 tau, lactate, CSF/serum albumin) into a subgroup. HT increased the risk for both PD and YOPD. In PD patients, but not in those with YOPD, the number of HTs directly correlated with CSF total-tau levels. No other correlations resulted between HT and clinical parameters. Sport-related HT was a specific risk factor for YOPD; conversely, the prolonged sporting life represented a protective factor. HTs can favor PD onset, even as YOPD. Sport-related HT resulted a risk factor for YOPD, although the longer sporting practice delayed PD onset, protecting from YOPD. Tauopathy may underlie the overall association between HT and PD. Additional mechanisms could be instead implicated in HT contribution to YOPD onset.

Association between physical activity and dementia's risk factors in patients with Parkinson's disease.

Evidence suggests that physical activity (PA) exerts beneficial effects on neurodegenerative processes, either as symptomatic relief or disease-modifying strategy. Actually, it may represent a viable neuroprotective intervention in Parkinson's disease dementia (PDD), a severe, frequent, and untreatable complication of Parkinson's disease (PD). According to such hypothesis, this cross-sectional study tested, in PD patients, the association between levels of PA and well-known risk factors for PDD, such as mood disorders and amyloid-ß42 CSF content. Amount of PA was measured by the International Physical Activity Questionnaires-Short Form (IPAQ-SF) in 128 cognitively intact PD patients and correlated with the Hamilton-Depression (HAM-D) and the Hamilton-Anxiety (HAM-A) scores; in a homogenous subgroup of 40 patients, it was further correlated with a panel of CSF biomarkers, including amyloid-ß42, total α-synuclein, total, and phosphorylated tau. The statistical model was corrected for the main potential confounding factors (motor impairment, dopaminergic treatment, disease duration, age, and sex). Both the HAM-A and HAM-D scores, as well as the Aß42 CSF content, improved in parallel with the increase of the total week amount of PA. Although with several limitations, we preliminarily demonstrated that a high level of PA is associated with a more favourable profile of PDD risk factors, in terms of both mood disturbances and CSF markers of neurodegeneration. However, confirmative studies are necessary to validate the efficacy of PA as protective intervention for PDD.

CSF Biomarkers for Early Diagnosis of Synucleinopathies: Focus on Idiopathic RBD.

PURPOSE OF REVIEW: Idiopathic REM sleep behavior disorder (iRBD) is one of the most significant prodromal manifestations of synucleinopathies. Different predictive biomarkers for iRBD conversion have been investigated, but scarce data are present in literature about the predictive role of cerebrospinal fluid (CSF) biomarkers. In this review, we focus on CSF biomarkers in patients with both iRBD and RBD associated with synucleinopathies to explore their potential predictive power. RECENT FINDINGS: Recent studies revealed that CSF α-synuclein levels are higher in Parkinson's disease (PD) patients with RBD compared to those without RBD, even if α-synuclein does not seem to predict conversion of iRBD into PD. In the Parkinson Progression Marker Initiative (PPMI) cohort, early PD patients with RBD show lower CSF Aß42 levels, which predict faster cognitive decline. CSF prion protein and inflammatory biomarkers have been also investigated in RBD and synucleinopathies with controversial results. A variety of CSF biomarkers are promising candidate for predicting iRBD conversion into synucleinopathies. Further studies are needed in iRBD patients followed for several years in order to observe the phenoconversion in synucleinopathies and to elucidate the possible role of CSF biomarkers as predictive biomarkers of conversion.

Neuropsychiatric symptoms differently affect mild cognitive impairment and Alzheimer's disease patients: a retrospective observational study.

Alzheimer's disease (AD) is the most common form of dementia characterized by the prevalent memory impairment. Mild cognitive impairment (MCI) may represent the early stage of AD, in particular when MCI patients show biomarkers consistent with AD pathology (MCI due to AD). Neuropsychiatric symptoms (NPS) frequently affect both MCI and AD patients. Cerebrospinal-fluid (CSF) tau and ß-amyloid42 (Aß42) levels are actually considered the most sensitive and specific biomarkers for AD neurodegeneration. In the present retrospective observational study, we evaluated CSF biomarkers and neuropsychological data (also including NPS measured by the neuropsychiatric inventory-NPI) in a population of patients affected by MCI due to AD compared with mild to moderate AD patients. We documented higher NPI scores in MCI compared with AD patients. In particular, sub-items related to sleep, appetite, irritability, depression, and anxiety were higher in MCI than AD. We also found the significant correlation between NPS and CSF AD biomarkers in the whole population of MCI and AD patients. Consistently, t-tau/Aß42 ratio correlated with NPS in all the MCI and AD patients. These results suggest the more prevalent occurrence of NPS in MCI patients showing AD pathology and converting to dementia than AD patients. Moreover, a more significant degree of AD neurodegeneration, featured by high t-tau/Aß42 ratio, correlated with more severe NPS, thus supposing that in MCI and AD patients a more extensive AD neurodegeneration is related to more severe behavioral disturbances.

Aggregation States of Aß1-40, Aß1-42 and Aßp3-42 Amyloid Beta Peptides: A SANS Study.

Aggregation states of amyloid beta peptides for amyloid beta A ß 1 - 40 to A ß 1 - 42 and A ß p 3 - 42 are investigated through small angle neutron scattering (SANS). The knowledge of these small peptides and their aggregation state are of key importance for the comprehension of neurodegenerative diseases (e.g., Alzheimer's disease). The SANS technique allows to study the size and fractal nature of the monomers, oligomers and fibrils of the three different peptides. Results show that all the investigated peptides have monomers with a radius of gyration of the order of 10 Å, while the oligomers and fibrils display differences in size and aggregation ability, with A ß p 3 - 42 showing larger oligomers. These properties are strictly related to the toxicity of the corresponding amyloid peptide and indeed to the development of the associated disease.

Cerebrospinal fluid biomarkers profile of idiopathic normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a disabling neurological disorder whose potential treatability is significantly limited by diagnostic uncertainty. In fact, typical clinical presentation occurs at late phases of disease, when CSF shunting could be ineffective. In recent years, measurement of different CSF proteins, whose concentration directly reflects neuropathological changes of CNS, has significantly improved both diagnostic timing and accuracy of neurodegenerative disease. Unfortunately iNPH lacks neuropathological hallmarks allowing the identification of specific disease biomarkers. However, neuropathology of iNPH is so rich and heterogeneous that many processes can be tracked in CSF, including Alzheimer's disease core pathology, subcortical degeneration, neuroinflammation and vascular dysfunction. Indeed, a huge number of CSF biomarkers have been analyzed in iNPH patients, but a unifying profile has not been provided yet. In this brief survey, we thus attempted to summarize the main findings in the field of iNPH CSF biomarkers, aimed at outlining a synthetic model. Although defined cut-off values for biomarkers are not available, a better knowledge of CSF characteristics may definitely assist in diagnosing the disease.

Clinical value of CSF amyloid-beta-42 and tau proteins in Progressive Supranuclear Palsy.

Progressive Supranuclear Palsy (PSP) is a four-repeat tauopathy with high phenotypic and neuropathological variability, highlighting the urgent need for effective disease biomarkers. Quantitative analysis of cerebrospinal fluid (CSF) proteins reflecting pathological changes of CNS is currently used as biomarkers of multiple neurodegenerative disorders for both early differential diagnosis and prognostic clustering of patients. In this study, we thus assessed the clinical usefulness of a panel of CSF biomarker in PSP patients presenting with Richardson's Syndrome. CSF levels of 42-beta-amyloid, total-tau, phosphorylated-tau, and both 42-beta-amyloid/phosphorylated-tau and phosphorylated-tau/total-tau ratios were comparatively evaluated in 39 PSP patients, 31 patients with Parkinson's Disease (PD) and 58 gender-/age-matched healthy controls. Specific gold-standard clinical scores were obtained. Diagnostic accuracy and clinical correlates of each biomarker were measured with receiver operating curve analysis and Spearman's test/linear regression, respectively. In PSP, 42-beta-amyloid was lower than either controls or PD; total-tau and phosphorylated-tau were instead reduced compared to controls, but similar to PD. At the cut-off value of 623 pg/ml, 42-beta-amyloid significantly distinguished PSP from controls and PD. Likewise, phosphorylated-tau/total-tau ratio also supported differential diagnosis between PSP and PD (cut-off = 0.185). 42-beta-amyloid was inversely associated with PSP severity, as measured with PSP Rating Scale. Our study demonstrates that CSF 42-beta-amyloid is reduced in PSP patients, proportionally to clinical severity, thus suggesting a potential use as disease biomarker. Moreover, phosphorylated-tau/total-tau ratio resulted helpful in the early differential diagnosis between PSP and PD.

Assessment of serum uric acid as risk factor for tauopathies.

Low levels of serum uric acid (UA) are a risk factor for many neurodegenerative diseases but the role of UA in tauopathies has not been yet fully evaluated. In this study, we assessed the risk associated with serum UA levels in a large group of patients with tauopathies, either primary or secondary. The mean serum UA concentrations of 111 patients with tauopathies (TAU), including 41 with progressive supranuclear palsy (PSP), 45 with Alzheimer's disease (AD) and 25 with frontotemporal dementia (FTD) were compared to that of 130 controls (CTL). The association between serum UA and TAU condition, PSP, AD and FTD was calculated as odd ratio (OR) adjusted for age and gender. A cut-off value of serum UA was finally obtained to predict subjects at risk for TAU. The serum UA levels in TAU and PSP, AD and FTD subgroups were similar, and significantly lower than CTL. Linear regression revealed inverse relationships between UA and TAU (OR = 0.610), PSP (OR = 0.626), AD (OR = 0.685) and FTD (OR = 0.577). The cut-off value of 4.35 mg/dl (AUC = 0.655) discriminates TAU from CTL, although with poor specificity and sensitivity. Low concentrations of serum UA represent a common risk factor for different tauopathies (PSP, FTD and AD). These findings may represent a starting point for preventive strategies or novel therapeutic approaches in this group of severe neurodegenerative diseases.

Levels of amyloid-beta-42 and CSF pressure are directly related in patients with Alzheimer's disease.

Experimental data suggest that the cerebrospinal fluid (CSF) dynamic is involved in the clearance of beta-amyloid, a key event in the pathogenesis of Alzheimer's disease (AD). At this regard no evidence still exists in vivo. In this study we explored the relationships between CSF pressure and AD pathology, as measured with CSF core biomarkers. We enrolled 16 patients with probable AD and 21 controls, collecting demographics, clinical data, CSF opening pressure and CSF levels of beta-amyloid-42 fragment (Aß42), total-tau (t-tau), phosphorylated-tau-181 (p-tau), albumin and albumin ratio. Differences between the groups were calculated with non-parametric tests, while correlations among all parameters were separately calculated with Spearman's test in each group. The groups significantly differed in biomarkers' concentration with lower Aß42, and higher t-tau and p-tau in AD patients. Moreover, CSF pressure was significantly lower in AD group (11.0 ± 2.8 vs. 13.3 ± 3.0 mmHg, p < 0.05) and directly correlated with Aß42 levels (R = 0.512; p < 0.05), but not with other biomarkers or parameters. No significant correlations emerged for biomarkers in control group. AD patients exhibit low CSF pressure whose values are directly and selectively related to CSF Aß42 levels. This interesting correlation may confirm in vivo the association between CSF dynamic and beta-amyloid metabolism occurring in AD.

Cerebrospinal fluid lactate levels and brain [18F]FDG PET hypometabolism within the default mode network in Alzheimer's disease.

PURPOSE: It has been suggested that neuronal energy metabolism may be involved in Alzheimer's disease (AD). In this view, the finding of increased cerebrospinal fluid (CSF) lactate levels in AD patients has been considered the result of energetic metabolism dysfunction. Here, we investigated the relationship between neuronal energy metabolism, as measured via CSF lactate levels, and cerebral glucose metabolism, as stated at the 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography ([18F]FDG PET) in AD patients. METHODS: AD patients underwent lumbar puncture to measure CSF lactate levels and [18F]FDG PET to assess brain glucose metabolism. CSF and PET data were compared to controls. Since patients were studied at rest, we specifically investigated brain areas active in rest-condition owing to the Default Mode Network (DMN). We correlated the CSF lactate concentrations with the [18F]FDG PET data in brain areas owing to the DMN, using sex, age, disease duration, Mini Mental State Examination, and CSF levels of tau proteins and beta-amyloid as covariates. RESULTS: AD patients (n = 32) showed a significant increase of CSF lactate levels compared to Control 1 group (n = 28). They also showed brain glucose hypometabolism in the DMN areas compared to Control 2 group (n = 30). Within the AD group we found the significant correlation between increased CSF lactate levels and glucose hypometabolism in Broadman areas (BA) owing to left medial prefrontal cortex (BA10, mPFC), left orbitofrontal cortex (BA11, OFC), and left parahippocampal gyrus (BA 35, PHG). CONCLUSION: We found high CSF levels of lactate and glucose hypometabolism within the DMN in AD patients. Moreover, we found a relationship linking the increased CSF lactate and the reduced glucose consumption in the left mPFC, OFC and PHG, owing to the anterior hub of DMN. These findings could suggest that neural glucose hypometabolism may affect the DMN efficiency in AD, also proposing the possible role of damaged brain energetic machine in impairing DMN.

A biological characterization of patients with postmenopausal Parkinson's disease.

Menopause increases the risk for Parkinson's disease (PD), although the underlying biological mechanisms have not been established in patients. Here, we aimed to understand the basis of menopause-related vulnerability to PD. Main motor and non-motor scores, blood levels of estradiol, testosterone, follicle-stimulating hormone, and luteinizing hormone, CSF levels of total α-synuclein, amyloid-ß-42, amyloid-ß-40, total tau, and phosphorylated-181-tau were examined in 45 women with postmenopausal-onset PD and 40 age-matched controls. PD patients had higher testosterone and lower estradiol levels than controls, and the residual estradiol production was associated with milder motor disturbances and lower dopaminergic requirements. In PD but not in controls, follicle-stimulating hormone levels correlated with worse cognitive scores and CSF markers of amyloidopathy and neuronal loss. In conclusion, menopause-related hormonal changes might differentially contribute to clinical-pathological trajectories of PD, accounting for the peculiar vulnerability to the disease.

Secondary neurodegeneration following Stroke: what can blood biomarkers tell us?

Stroke is one of the leading causes of death and the primary source of disability in adults, resulting in neuronal necrosis of ischemic areas, and in possible secondary degeneration of regions surrounding or distant to the initial damaged area. Secondary neurodegeneration (SNDG) following stroke has been shown to have different pathogenetic origins including inflammation, neurovascular response and cytotoxicity, but can be associated also to regenerative processes. Aside from focal neuronal loss, ipsilateral and contralateral effects distal to the lesion site, disruptions of global functional connectivity and a transcallosal diaschisis have been reported in the chronic stages after stroke. Furthermore, SNDG can be observed in different areas not directly connected to the primary lesion, such as thalamus, hippocampus, amygdala, substantia nigra, corpus callosum, bilateral inferior fronto-occipital fasciculus and superior longitudinal fasciculus, which can be highlighted by neuroimaging techniques. Although the clinical relevance of SNDG following stroke has not been well understood, the identification of specific biomarkers that reflect the brain response to the damage, is of paramount importance to investigate in vivo the different phases of stroke. Actually, brain-derived markers, particularly neurofilament light chain, tau protein, S100b, in post-stroke patients have yielded promising results. This review focuses on cerebral morphological modifications occurring after a stroke, on associated cellular and molecular changes and on state-of-the-art of biomarkers in acute and chronic phase. Finally, we discuss new perspectives regarding the implementation of blood-based biomarkers in clinical practice to improve the rehabilitation approaches and post stroke recovery.

Neutrophil-to-lymphocyte ratio and lymphocyte count reflect alterations in central neurodegeneration-associated proteins and clinical severity in Parkinson Disease patients.

INTRODUCTION: Peripheral inflammation has been recently associated to Parkinson disease (PD). However, how the peripheral inflammatory immune response could affect the clinical-pathological features of the disease is not fully understood. In this study, we assessed the peripheral immune profile of a well-characterized PD cohort, examining several correlations with CSF biomarkers of neurodegeneration and the main clinical parameters, aimed at better elucidating the complex dynamics of the brain-periphery interactions in PD. METHODS: The leukocyte populations counts (neutrophils, lymphocytes, monocytes, eosinophils, and basophils) and the neutrophil-to-lymphocyte ratio (NLR) were collected and compared in 61 PD patients and 60 sex/age matched controls (CTRLs). Immune parameters were correlated with CSF levels of total α-synuclein, amyloid-ß-42, total and phosphorylated-tau and main motor and non-motor scores. RESULTS: PD patients had lower lymphocyte and higher NLR counts compared to CTRLs. In PD patients, the lymphocyte count directly correlated with CSF α-synuclein levels, whereas NLR displayed an inverse correlation with the CSF amyloid-ß42 levels. The lymphocyte count also negatively correlated with HY stage, while NLR positively with the disease duration. CONCLUSIONS: This study provided in vivo evidence that, in PD, changes in leukocytes in the periphery, assessed as relative lymphopenia and NLR increase, reflect in central neurodegeneration-associated proteins modifications, especially in α-synuclein and amyloid-ß pathways, and greater clinical burden.

Clinical and neurochemical correlates of the APOE genotype in early-stage Parkinson's disease.

Emerging evidence indicates that apolipoprotein E (APOE) genotype may influence Parkinson's disease (PD) course, although clinical and neurochemical correlates have not been completely established. This study aimed to determine the associations of APOE genotypes (ε4 vs. non-ε4) with cerebrospinal fluid (CSF) neurodegeneration biomarkers and clinical parameters in early-stage PD patients. One hundred and seventy-five PD patients and 89 non-neurodegenerative controls grouped in APOE-ε4 carriers (28 PD; 12 controls) and non-APOE-ε4 carriers (147 PD; 78 controls) were enrolled. CSF levels of amyloid-ß-42, amyloid-ß-40, total and 181-phosphorylated tau, and clinical scores were compared among groups adjusting for main covariates. APOE genotypes prevalence was similar in PD and controls. PD APOE-ε4 carriers had lower amyloid-ß-42 CSF levels than PD non-APOE-ε4 carriers and controls, independently from age. PD APOE-ε4 carriers also had higher total and "item 5" (attention and memory) non-motor symptoms scale scores than PD non-APOE-ε4 carriers, independently from confounding factors. APOE-ε4 genotype might thus account for a more vulnerable PD subtype characterized by prominent amyloidopathy and a greater burden of non-motor symptoms in the early disease stages. DATA AVAILABILITY: Data are available upon reasonable request.

Cerebrospinal fluid levels of Aß42 relationship with cholinergic cortical activity in Alzheimer's disease patients.

The dysfunction of cholinergic neurons is a typical hallmark in Alzheimer's disease (AD). In animal models of AD, fragments of amyloid beta protein (Aß) and Tau protein are thought to interfere with central cholinergic transmission, specifically with synthesis and release of acetylcholine. Thus, we aimed to investigate whether the cerebrospinal fluid (CSF) levels of Aß42 and Tau proteins in AD patients could influence physiological central cholinergic activity. In AD patients (n = 19), central cholinergic function was evaluated in vivo by using short afferent latency inhibition (SLAI), and compared to age-matched healthy controls. In the same AD patients, CSF samples were collected through lumbar puncture to obtain individual levels of Aß42, total Tau (t-Tau) and phosphorylated Tau (p-Tau) (Thr181). SLAI was decreased in AD patients in comparison to age-matched healthy controls. We found that in patients there was a negative correlation between the individual amount of cholinergic activity assessed by SLAI and the CSF levels of Aß42. On the other hand, there was a positive correlation between the levels of SLAI and CSF p-Tau. No correlation was found when SLAI was analysed together with t-Tau. These results demonstrate that mechanisms of cortical cholinergic activity are altered in patients bearing a pathological CSF hallmark of AD, suggesting that these peptides may have some influence on the cholinergic dysfunction in AD. We suggest that coupling of CSF biomarkers with neurophysiological parameters of central cholinergic function could be important to better detect ongoing mechanisms of neural degeneration in vivo.

Constipation distinguishes different clinical-biochemical patterns in de novo Parkinson's disease.

INTRODUCTION: Prodromal constipation (PC) at Parkinson's disease (PD) onset may mark a distinct neurodegenerative trajectory; accordingly, presenting phenotype, biochemical signature, and progression of PD patients with PC (PD + PC) might differ from those without (PDwoPC). We compared the clinical-biochemical profile of de novo PD patients with and without PC, and the respective mid-term progression, to establish the grouping effect of PC. METHODS: Motor and non-motor scores were collected at diagnosis in n = 57 PD + PC patients and n = 73 PDwoPC. Paired CSF biomarkers (α-synuclein, amyloid and tau peptides, lactate, CSF/serum albumin ratio or AR) were assessed into a smaller sample and n = 46 controls. Clinical progression was estimated as Hoehn and Yahr stage (HY) and levodopa equivalent daily dose (LEDD) change 2.06 ± 1.35 years after diagnosis. RESULTS: At onset, PD + PC patients had higher HY and MDS-UPDRS-part III scores, and higher CSF AR. PDwoPC had higher Non-Motor Symptoms Scale domain-2 score, and lower CSF α-synuclein level. At follow-up, PD + PC had greater LEDD. CONCLUSIONS: PC identifies a group of de novo patients with more severe motor impairment, possible blood brain barrier disruption, and greater dopaminergic requirement at mid-term; conversely, de novo PDwoPC patients had prominent fatigue, and pronounced central synucleinopathy.

Tau and Amyloid-ß Peptides in Serum of Patients With Parkinson's Disease: Correlations With CSF Levels and Clinical Parameters.

Relevance of blood-based biomarkers is increasing into the neurodegenerative diseases field, but data on Parkinson's disease (PD) remain still scarce. In this study, we used the SiMoA technique to measure serum content of total tau protein and amyloid-ß peptides (Aß-42, Aß-40) in 22 PD patients and ten control subjects. Serum levels of each biomarker were correlated with the respective CSF levels in both the groups; in PD patients, also the correlations between serum biomarkers and main clinical parameters were tested (motor, non-motor, cognitive scores and levodopa equivalent daily dose). Serum biomarkers did not exhibit quantitative differences between patients and controls; however, only PD patients had inter-fluids (serum-CSF) associations in tau and amyloid-ß-42 levels. Moreover, serum content of tau protein was inversely correlated with cognitive performances (MoCA score). These findings, albeit preliminary, indicate that brain-derived peptides may change in parallel in both peripheral blood and CSF of PD patients, eventually even in association with some clinical features. Further studies are now needed to validate the use of blood-based biomarkers in PD.

How Comorbidity Reflects on Cerebrospinal Fluid Biomarkers of Neurodegeneration in Aging.

Systemic comorbidity precipitates the risk for dementia. To comprehend the underlying mechanisms into a therapeutic perspective, we analyzed how comorbidity affects neurodegeneration-related cerebrospinal fluid (CSF) biomarkers of 55 cognitively intact subjects. The Charson Comorbidity Index (CCI) was correlated with CSF amyloid-ß42 (Aß42), amyloid-ß40, total-tau, 181-phosphorylated-tau (p-tau), the Aß42/p-tau ratio, neurogranin, and lactate. The age-related brain lesions at imaging were also considered. CCI had a raw association with Aß42/p-tau and p-tau, and a stronger, age-independent correlation with lactate. These preliminary findings suggested that, in normal subjects, systemic comorbidity might increase CNS oxidative stress and, together with aging, contribute to develop an Alzheimer's disease-like biochemical profile.