Lack of Association between CD33 rs3865444 and Amyotrophic Lateral Sclerosis: A Case-Control Study.

BACKGROUND: Microglial activation is considered to assume a role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). To date, the relationship between ALS and the rs3865444 polymorphism of the cluster of differentiation 33 (CD33) has not been explored. The current report aimed to investigate the potential connection between CD33 rs3865444 and ALS. METHODS: Patients diagnosed with sporadic ALS according to the revised El Escorial criteria, as well as age and sex matched community controls, were enrolled. Two evenly numbered, age and sex matched groups of 155 participants each were genotyped. RESULTS: No association was found between rs3865444 and ALS [log-additive odds ratio (OR) = 0.83 (0.57, 1.22), over-dominant OR = 0.86 (0.55, 1.36), recessive OR = 0.73 (0.25, 2.17), dominant OR = 0.82 (0.52, 1.29), co-dominant OR1 = 0.68 (0.23, 2.05) and co-dominant OR2 = 0.84 (0.53, 1.33)]. Moreover, no relationship was established between rs3865444 and the age of ALS onset based on both unadjusted and sex adjusted Cox-proportional hazards models. Finally, no association between rs3865444 and ALS was found in subgroup analyses based on the site of ALS onset (bulbar or spinal) and sex. CONCLUSIONS: The current analysis is the first to report that rs3865444 is not linked to ALS. Larger multi-racial studies are required to confirm these findings.

Cortical involvement and leptomeningeal inflammation in myelin oligodendrocyte glycoprotein antibody disease: A three-dimensional fluid-attenuated inversion recovery MRI study.

BACKGROUND: Cortical demyelination and meningeal inflammation have been detected neuropathologically in multiple sclerosis (MS) and recently in myelin oligodendrocyte glycoprotein antibody disease (MOGAD). OBJECTIVES: To assess in vivo cortical and leptomeningeal involvement in MOGAD. METHODS: We prospectively evaluated 11 MOGAD and 12 relapsing-remitting MS (RRMS) patients combining three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) and 3D-T1-weighted (3D-T1w) sequences at 3-Tesla magnetic resonance imaging (MRI). Leptomeningeal contrast enhancement (LMCE) was assessed on 3D-FLAIR post-gadolinium (3D-FLAIRGd). Cerebral cortical lesions (CCLs) were classified as either intracortical-subpial (IC-SP) or leukocortical (LC). RESULTS: CCLs were present in 8/11 MOGAD and 12/12 RRMS patients, with the number of CCLs being significantly lower in MOGAD (median (interquartile range (IQR)) 3 (0.5-4) vs 12 (4.75-19), p = 0.0032). In MOGAD, IC-SP lesions were slightly more prevalent than LC lesions (2 (0-2.5) vs 1 (0-2), p = 0.6579); whereas in RRMS, IC-SP lesions were less prevalent than LC lesions (3.5 (2.75-5.5) vs 9 (2-12.75), p = 0.27). LMCE was observed in 3/11 MOGAD and 1/12 RRMS patients; MOGAD with LMCE showed an increased median number of CCLs compared with MOGAD without LMCE (8 (4-9) vs 2.5 (0.75-3.25), p = 0.34). No correlation was observed between MOGAD MRI findings and (a) MOGAD duration, (b) serum MOG-immunoglobulin G1 titers, and (c) oligoclonal band presence. CONCLUSION: We described cortical lesion topography and detected for the first time LMCE using 3D-FLAIRGd sequences in MOGAD patients.

Lack of association between TREM2 rs75932628 variant and amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease. Inflammatory processes are among the mechanisms that are implicated in ALS pathogenesis. The TREM2 rs75932628 T variant may influence the regulatory effect of TREM2 on inflammation. Studies regarding the role of the rs75932628 variant in ALS have yielded inconsistent results, so far. To assess the role of TREM2 rs75932628 on ALS risk. We genotyped 155 patients with sporadic ALS and 155 healthy controls for TREM2 rs75932628. We also merged and meta-analyzed our data with data from previous studies (with a total of 7524 ALS cases and 14,675 controls), regarding TREM2 rs75932628 and ALS. No ALS or healthy subjects carried the TREM2 rs75932628-T variant. Results from meta-analyses (overall approach and sensitivity analyses) yielded no significant results for possible connection between TREM2 rs75932628-T variant and ALS. Based on our results, TREM2 rs75932628 does not seem to play a determining role to the pathophysiology of ALS.

CYP1A2 rs762551 polymorphism and risk for amyotrophic lateral sclerosis.

BACKGROUND: Genetic variability is considered to confer susceptibility to amyotrophic lateral sclerosis (ALS). Oxidative stress is a significant contributor to ALS-related neurodegeneration, and it is regulated by cytochromes P450 (CYPs), such as CYP1A2; these are responsible for the oxidative metabolism of both exogenous and endogenous substrates in the brain, subsequently impacting ALS. The function of CYP1A2 is largely affected by genetic variability; however, the impact of CYP1A2 polymorphisms in ALS remains underinvestigated. OBJECTIVE: This study aims to examine the possible association of ALS with the CYP1A2 rs762551 polymorphism, which codes for the high inducibility form of the enzyme. METHODS: One hundred and fifty-five patients with sporadic ALS and 155 healthy controls were genotyped for the CYP1A2 rs762551. Statistical testing for the association of CYP1A2 rs762551 with risk for ALS was performed using SNPstats. RESULTS: The CYP1A2 rs762551 C allele was associated with a decreased risk of ALS development. In the subgroup analysis according to the ALS site of onset, an association between CYP1A2 rs762551 and limb and bulbar onset of ALS was shown. Cox proportional-hazard regression analyses revealed a significant effect of the CYP1A2 rs762551 on the age of onset of ALS. CONCLUSIONS: Based on our results, a primarily potential link between the CYP1A2 rs762551 polymorphism and ALS risk could exist.

MOBP rs616147 Polymorphism and Risk of Amyotrophic Lateral Sclerosis in a Greek Population: A Case-Control Study.

Background and Objectives: To date, only one study has investigated the association between the rs616147 polymorphism of the Myelin-associated Oligodendrocyte Basic Protein (MOBP) locus and Amyotrophic Lateral Sclerosis (ALS). Materials and Methods: A case-control study was performed. Patients with definite sporadic ALS were prospectively and consecutively recruited from the inpatient and outpatient clinics of the Neurology Department of the General University Hospital of Larissa, Central Greece. Community based, age and sex matched healthy individuals with a free personal and family history constituted the control group. Results: A total of 155 patients with definite sporadic ALS and an equal number of healthy controls were genotyped. The power of our sample size was slightly above 80% and MOBP rs616147 was determined to be in Hardy-Weinberg Equilibrium among healthy participants (p = 1.00). According to the univariate analysis, there was no significant relationship between rs616147 and ALS [log-additive OR = 0.85 (0.61, 1.19), over-dominant OR = 0.73 (0.46, 1.15), recessive OR = 1.02 (0.50, 2.09), dominant OR = 0.74 (0.47, 1.16), co-dominant OR1 = 0.71 (0.44, 1.14) and co-dominant OR2 = 0.88 (0.42, 1.84). Additionally, the effect of rs616147 on the age of ALS onset was determined insignificant using both unadjusted and adjusted (sex, site of onset) cox-proportional models. Finally, rs616147 was not related to the site of ALS onset. Conclusions: Our study is the first to report the absence of an association between MOBP rs616147 and ALS among individuals of Greek ancestry. Additional, larger nationwide and multi-ethnic studies are warranted to shed light on the connection between rs616147 and ALS.

Defective synaptic connectivity and axonal neuropathology in a human iPSC-based model of familial Parkinson's disease.

α-Synuclein (αSyn) is the major gene linked to sporadic Parkinson's disease (PD), whereas the G209A (p.A53T) αSyn mutation causes a familial form of PD characterized by early onset and a generally severe phenotype, including nonmotor manifestations. Here we generated de novo induced pluripotent stem cells (iPSCs) from patients harboring the p.A53T mutation and developed a robust model that captures PD pathogenic processes under basal conditions. iPSC-derived mutant neurons displayed novel disease-relevant phenotypes, including protein aggregation, compromised neuritic outgrowth, and contorted or fragmented axons with swollen varicosities containing αSyn and Tau. The identified neuropathological features closely resembled those in brains of p.A53T patients. Small molecules targeting αSyn reverted the degenerative phenotype under both basal and induced stress conditions, indicating a treatment strategy for PD and other synucleinopathies. Furthermore, mutant neurons showed disrupted synaptic connectivity and widespread transcriptional alterations in genes involved in synaptic signaling, a number of which have been previously linked to mental disorders, raising intriguing implications for potentially converging disease mechanisms.

ERCC6L2 rs591486 polymorphism and risk for amyotrophic lateral sclerosis in Greek population.

BACKGROUND: Α number of genetic variants have been associated with amyotrophic lateral sclerosis (ALS). A recent study supports that rs591486 across the ERCC6L2 gene and exposure to pesticides seem to have a joint effect on the development of Parkinson's disease, a disease which shares a few common characteristics with ALS. OBJECTIVE: To detect a possible contribution of rs591486 ERCC6L2 to ALS. METHODS: A total of 155 patients with ALS and 155 healthy controls were included in the study and genotyped for rs591486. Using logistic regression analyses (crude and adjusted for age and sex), rs591486 was tested for association with ALS risk. Subgroup analysis based on ALS site of onset was also performed. Cox regression analysis was applied in order for the effect of ERCC6L2 rs591486 on ALS age of onset to be tested. RESULTS: Adjusted analysis showed that ERCC6L2 rs591486 was associated with an increased risk of ALS development, in dominant [odds ratio, OR (95% confidence interval, CI) 2.15 (1.04-4.46), p = 0.037] and over-dominant [OR (95%CI) = 1.91 (1.01-3.60), p = 0.043], modes. Subgroup analysis based on ALS site of onset revealed an association between ERCC6L2 rs591486 and ALS with limb onset. Results for Cox regression analysis indicated that G/A carriers had a lower age of ALS limb onset when compared to G/G carriers. CONCLUSIONS: The current study provides preliminary indication for an implication of ERCC6L2 rs591486 in ALS development, as a possible genetic risk factor. These results possibly suggest that oxidative stress may be the main contributor in the pathophysiology of ALS.

123I-FP-CIT SPECT [(123) I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] Imaging in a p.A53T α-synuclein Parkinson's disease cohort versus Parkinson's disease.

BACKGROUND: The p.A53T point mutation in the α-synuclein gene (SNCA) is a rare but highly relevant cause of autosomal dominant Parkinson's disease (PD). OBJECTIVES: The objective of this study was to assess striatal dopaminergic denervation in a cohort of symptomatic carriers of the p.A53T SNCA mutation as compared to PD patients. METHODS: Data from the Parkinson's Progression Markers Initiative database of 11 symptomatic p.A53T SNCA mutation carriers who underwent 123I-FP-CIT SPECT [(123) I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] imaging at our site were compared with those of 33 age-, sex-, and disease duration-matched PD patients. RESULTS: The p.A53T mutation carriers had significantly lower caudate nucleus binding ratio both contralaterally and ipsilaterally to the most affected side (P = .002 and P = .006) and a decreased contralateral caudate/putamen signal ratio (P = .007) as compared to PD. A similar degree of striatal asymmetry was observed in both subgroups. No correlation between scores in neuropsychological tests and caudate nucleus dopaminergic denervation could be demonstrated. CONCLUSIONS: PD patients harboring the p.A53T SNCA mutation show evidence of a more severe nigrostriatal denervation, especially evident in the caudate nucleus. The lack of significant differences in the putaminal binding ratios may reflect a floor effect or a true preferential targeting of the caudate terminals in p.A53T SNCA-associated PD. © 2018 International Parkinson and Movement Disorder Society.

Is spinal muscular atrophy a disease of the motor neurons only: pathogenesis and therapeutic implications?

Spinal muscular atrophy (SMA) is a genetic neurological disease that causes infant mortality; no effective therapies are currently available. SMA is due to homozygous mutations and/or deletions in the survival motor neuron 1 gene and subsequent reduction of the SMN protein, leading to the death of motor neurons. However, there is increasing evidence that in addition to motor neurons, other cell types are contributing to SMA pathology. In this review, we will discuss the involvement of non-motor neuronal cells, located both inside and outside the central nervous system, in disease onset and progression. Even if SMN restoration in motor neurons is needed, it has been shown that optimal phenotypic amelioration in animal models of SMA requires a more widespread SMN correction. It has been demonstrated that non-motor neuronal cells are also involved in disease pathogenesis and could have important therapeutic implications. For these reasons it will be crucial to take this evidence into account for the clinical translation of the novel therapeutic approaches.

Motor and Nonmotor Features of Carriers of the p.A53T Alpha-Synuclein Mutation: A Longitudinal Study.

BACKGROUND: G209A SNCA mutation carriers represent an important group of genetic PD. We describe motor and nonmotor features of G209A SNCA mutation carriers. METHODS: Longitudinal clinical assessments over 2 years were collected in 22 symptomatic and 8 asymptomatic G209A SNCA mutation carriers. Motor and nonmotor rating scales were administered. Correlations were performed between clinical variables and disease duration or age. Penetrance was calculated using Kaplan-Meier survival curves. RESULTS: Asymptomatic carriers did not manifest clear premotor symptoms, but symptomatic carriers often reported that olfactory dysfunction and rapid eye movement sleep behavior disorder preceded motor symptoms. Prominent motor decline and deterioration of autonomic and cognitive function occurred at follow-up; such nonmotor features correlated with disease duration, but not age. Disease penetrance was estimated at around 90%. CONCLUSIONS: This study may help to inform clinical trials and provide the basis for studies of disease modifiers in genetic synucleinopathy cohorts. © 2016 International Parkinson and Movement Disorder Society.

Lysosomal alterations in peripheral blood mononuclear cells of Parkinson's disease patients.

BACKGROUND: Reduced expression of lysosomal-associated membrane protein 2a and heatshock-cognate 70 proteins, involved in chaperone-mediated autophagy and of glucocerebrosidase, is reported in PD brains. The aim of this study was to identify systemic alterations in lysosomal-associated membrane protein 2a, heatshock cognate-70, and glucocerebrosidase levels/activity in peripheral blood mononuclear cells from PD patients. METHODS: Protein/mRNA levels were assessed in PD patients from genetically undetermined background, alpha-synuclein (G209A/A53T), or glucocerebrosidase mutation carriers and age-/sex-matched controls. RESULTS: Heatshock cognate 70 protein levels were reduced in all PD groups, whereas its mRNA levels were decreased only in the genetically undetermined group. Glucocerebrosidase protein levels were decreased only in the genetic PD groups, whereas increased mRNA levels and decreased activity were detected only in the glucocerebrosidase mutation group. CONCLUSIONS: Reduced heatshock cognate-70 levels are suggestive of an apparent systemic chaperone-mediated autophagy dysfunction irrespective of genetic background. Glucocerebrosidase activity may serve as a screening tool to identify glucocerebrosidase mutation carriers with PD.

Genomic and transcriptomic advances in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder and the most common motor neuron disease. ALS shows substantial clinical and molecular heterogeneity. In vitro and in vivo models coupled with multiomic techniques have provided important contributions to unraveling the pathomechanisms underlying ALS. To date, despite promising results and accumulating knowledge, an effective treatment is still lacking. Here, we provide an overview of the literature on the use of genomics, epigenomics, transcriptomics and microRNAs to deeply investigate the molecular mechanisms developing and sustaining ALS. We report the most relevant genes implicated in ALS pathogenesis, discussing the use of different high-throughput sequencing techniques and the role of epigenomic modifications. Furthermore, we present transcriptomic studies discussing the most recent advances, from microarrays to bulk and single-cell RNA sequencing. Finally, we discuss the use of microRNAs as potential biomarkers and promising tools for molecular intervention. The integration of data from multiple omic approaches may provide new insights into pathogenic pathways in ALS by shedding light on diagnostic and prognostic biomarkers, helping to stratify patients into clinically relevant subgroups, revealing novel therapeutic targets and supporting the development of new effective therapies.

Changes of trans and saturated fatty acid content in savory baked goods from 2015 to 2021 and their effect on consumers' intake using substitution models: A study conducted in Greece.

BACKGROUND: In Greece, nearly a third of savory baked goods (SBGs) exceeded the limit of 2 g of nonruminant or industrial trans fatty acids (i-TFA) per 100 g fat in 2015. The impact of the Commission Regulation (European Union) 2019/649 on exposure to trans fatty acids (TFA), i-TFA, and saturated fatty acid (SFA) from SBGs has not been previously evaluated. OBJECTIVES: The study aimed to explore fatty acid reformulation of SBG products and assess differences in TFA, i-TFA, and SFA intakes using a sample of Greek SBG consumers from a nationally representative survey. METHODS: In 2021, 140 samples of SBGs were collected in the greater metropolitan area of Athens, and their fat profile and content were compared to those from 2015. Based on these measurements, food consumption substitution models were employed to examine TFA and SFA intake differences, and the percent contribution from SBG among consumers was calculated (N = 1008). Nutrient densities were calculated by adjusting all fat intakes by individual mean energy intake (percentage of daily total energy intake). RESULTS: The 2% i-TFA legislative limit/100 g of fat in measured SBGs was exceeded by 11.4% in 2021 compared to 31.1% in 2015 (19.7% increase in compliance). Median i-TFA and TFA intakes from SBGs were reduced from 0.05 (0.01, 0.12)% and 0.13 (0.03, 0.27)% in 2015 to 0.03 (0.01, 0.09) and 0.06 (0.03, 0.13)% in 2021, respectively. In terms of SFA, a mean increase/100 g was calculated, resulting in an increased intake in 2021 compared to 2015 [5.18% (2.78, 8.37) and 3.55 (1.99, 5.73), respectively]. CONCLUSIONS: Despite the reductions seen in i-TFA content of SBGs, food product reformulation efforts in Greece should focus not only on TFA content but also on SFA reduction to improve public health.

Serum Uric Acid as a Putative Biomarker in Prodromal Parkinson's Disease: Longitudinal Data from the PPMI Study.

BACKGROUND: The role of blood uric acid as a biomarker in symptomatic motor PD has been increasingly established in the literature. OBJECTIVE: Our present study assessed the role of serum uric acid as a putative biomarker in a prodromal PD cohort [REM Sleep Behavior disorder (RBD) and Hyposmia] followed longitudinally. METHODS: Longitudinal 5-year serum uric acid measurement data of 39 RBD patients and 26 Hyposmia patients with an abnormal DATSCAN imaging were downloaded from the Parkinson's Progression Markers Initiative database. These cohorts were compared with 423 de novo PD patients and 196 healthy controls enrolled in the same study. RESULTS: After adjusting for age, sex, body mass index, and concomitant disorders (hypertension/gout), baseline and longitudinal serum uric acid levels were higher in the RBD subgroup as compared to the established PD cohort (p = 0.004 and p = 0.001). (Baseline RBD 6.07±1.6 vs. Baseline PD 5.35±1.3 mg/dL and Year-5 RBD 5.7±1.3 vs. Year-5 PD 5.26±1.33). This was also true for longitudinal measurements in the Hyposmic subgroup (p = 0.008) (Baseline Hyposmic 5.7±1.6 vs. PD 5.35±1.3 mg/dL and Year-5 Hyposmic 5.58±1.6 vs. PD 5.26±1.33). CONCLUSION: Our results indicate that serum uric acid levels are higher in prodromal PD subjects with ongoing dopaminergic degeneration compared to those with manifest PD. These data indicate that the well-established decrease in the levels of serum uric acid occurs with the transition from prodromal to clinical PD. Whether the higher levels of serum uric acid observed in prodromal PD may provide protection against conversion to full-blown clinical PD will require further study.

Evidence of an association between the scavenger receptor class B member 2 gene and Parkinson's disease.

Lysosomal protein 2 (LIMP2), the product of the scavenger receptor class B member 2 (SCARB2) gene, is a ubiquitously expressed transmembrane protein that is the mannose-6-phosphate-independent receptor for glucocerebrosidase (ß-GCase); a deficiency in this protein causes Gaucher disease. Several studies have shown a link between mutations in the ß-GCase gene and diseases characterized clinically by Parkinsonism and by the presence of Lewy body-related pathology. We hypothesized that genetic variants in the SCARB2 gene could be risk factors for Parkinson's disease (PD). A candidate-gene study of 347 Greek patients with sporadic PD and 329 healthy controls was conducted to investigate the association between 5 polymorphisms in the SCARB2 gene (rs6824953, rs6825004, rs4241591, rs9991821, and rs17234715) and the development of PD. The single-locus analysis for the 5 polymorphisms revealed an association only for the rs6825004 polymorphism: the generalized odds ratio (OR(G) ) was 0.68 (95% confidence interval [CI], 0.51-0.90), and the OR for the allelic test was OR = 0.71 (95% CI, 0.56-0.90). Haplotype analysis showed an association for the GCGGT haplotype (P < .01). Our study supports a genetic contribution of the SCARB2 locus to PD; future studies in larger cohorts are necessary to verify this finding.

Engineering of Optical and Electrical Properties of Electrodeposited Highly Doped Al:ZnO and In:ZnO for Cost-Effective Photovoltaic Device Technology.

Resistivity and transparency of zinc-oxide layers (ZnO) for chalcopyrite photovoltaic technology applications were engineered by activation of the Burstein-Moss (BM) effect at high concentrations of aluminium (Al) and indium (In) dopant. The Al:ZnO and In:ZnO layers were processed by cost-effective, large-area, fast-rate electrochemical deposition techniques from aqueous solution of zinc nitrate (Zn(NO3)2) and dopant trichlorides, at negative electrochemical potential of EC = (-0.8)-(-1.2) V, moderate temperature of 80 °C, and solute dopant concentrations of AlCl3 and InCl3 up to 20 and 15 mM, respectively. Both Al:ZnO and In:ZnO layers were deposited on Mo/glass substrates with ZnO and ZnO/ZnSe buffers (Al:ZnO/ZnO/Mo/glass, In:ZnO/ZnO/ZnSe/Mo/glass), respectively. Based on the band-gap energy broadening of Al:ZnO and In:ZnO originated by the BM effect, maximum carrier concentrations of the order 1020 and 1021 cm-3, respectively, were determined by optical characterization techniques. The (electrical) resistivity values of Al:ZnO calculated from optical measurements were commensurate with the results of electrical measurements (10-4 Ohm·cm). In both cases (Al:ZnO and In:ZnO), calibration of carrier density in dependence of solute dopant concentration (AlCl3 and InCl3) was accomplished. The p-n junctions of Au/In:ZnO/ZnO/ZnSe/CIGS/Mo on glass substrate exhibited current-voltage (I-V) characteristics competing with those of crystalline silicon (c-Si) solar cells.

Distinct profiles of LRRK2 activation and Rab GTPase phosphorylation in clinical samples from different PD cohorts.

Despite several advances in the field, pharmacodynamic outcome measures reflective of LRRK2 kinase activity in clinical biofluids remain urgently needed. A variety of targets and approaches have been utilized including assessments of LRRK2 itself (levels, phosphorylation), or its substrates (e.g. Rab10 or other Rab GTPases). We have previously shown that intrinsic kinase activity of LRRK2 isolated from PBMCs of G2019S carriers is elevated, irrespective of disease status. In the present study we find that phosphorylation of Rab10 is also elevated in G2019S carriers, but only those with PD. Additionally, phosphorylation of this substrate is also elevated in two separate idiopathic PD cohorts, but not in carriers of the A53T mutation in α-synuclein. In contrast, Rab29 phosphorylation was specifically reduced in urinary exosomes from A53T and idiopathic PD patients. Taken together, our findings highlight the need for the assessment of multiple complimentary targets for a more comprehensive picture of the disease.

Lipid level alteration in human and cellular models of alpha synuclein mutations.

Lipid profiles in biological fluids from patients with Parkinson's disease (PD) are increasingly investigated in search of biomarkers. However, the lipid profiles in genetic PD remain to be determined, a gap of knowledge of particular interest in PD associated with mutant α-synuclein (SNCA), given the known relationship between this protein and lipids. The objective of this research is to identify serum lipid composition from SNCA A53T mutation carriers and to compare these alterations to those found in cells and transgenic mice carrying the same genetic mutation. We conducted an unbiased lipidomic analysis of 530 lipid species from 34 lipid classes in serum of 30 participants with SNCA mutation with and without PD and 30 healthy controls. The primary analysis was done between 22 PD patients with SNCA+ (SNCA+/PD+) and 30 controls using machine-learning algorithms and traditional statistics. We also analyzed the lipid composition of human clonal-cell lines and tissue from transgenic mice overexpressing the same SNCA mutation. We identified specific lipid classes that best discriminate between SNCA+/PD+ patients and healthy controls and found certain lipid species, mainly from the glycerophosphatidylcholine and triradylglycerol classes, that are most contributory to this discrimination. Most of these alterations were also present in human derived cells and transgenic mice carrying the same mutation. Our combination of lipidomic and machine learning analyses revealed alterations in glycerophosphatidylcholine and triradylglycerol in sera from PD patients as well as cells and tissues expressing mutant α-Syn. Further investigations are needed to establish the pathogenic significance of these α-Syn-associated lipid changes.

Asymptomatic carriers of the p.A53T SNCA mutation: Data from the PPMI study.

We assessed non motor characteristics of 12 asymptomatic p.A53T mutation carriers (A53T-AC) compared with 36 healthy controls (HC) enrolled in the Parkinson's Progression Markers Initiative (PPMI) study. Olfaction score was lower and anxiety was marginally more prevalent in A53T- AC. These findings suggest distinct prodromal features in this group of subjects.