Differentiating progressive supranuclear palsy from other movement disorders using transcranial sonography: a systematic review and meta-analysis.

Progressive supranuclear palsy (PSP) is an atypical parkinsonism that presents with different phenotypes. There are still no validated diagnostic biomarkers for early diagnosis of PSP. Transcranial sonography (TCS) is a promising tool in the differential diagnosis of parkinsonian disorders; however, there are no systematic investigations about the application of TCS in PSP patients. Therefore, we performed a systematic review and meta-analysis to discuss the role of TCS in diagnosing PSP by systematically searching PubMed, Cochrane Library, Chinese National Knowledge Infrastructure and Wan Fang databases. Of 66 obtained records, 16 articles, including 366 patients with PSP, were included. Our results showed the estimated random-effects pooled prevalence of substantia nigra hyperechogenicity in patients with PSP was 22% (95% CI 12-32%), lenticular nucleus hyperechogenicity was 70% (95% CI 52-82%), and enlarged third ventricle was 71% (95% CI 55-85%). Additionally, a normal echogenicity substantia nigra in TCS showed 70% sensitivity (95% CI 56-81%) and 86% specificity (95% CI 75-86%) to differentiate PSP from Parkinson's disease. In conclusion, TCS is an important supplementary biomarker for diagnosing PSP. At the same time, the diagnostic value of TCS in discriminating PSP from other atypical parkinsonism and between different PSP phenotypes needs further exploration.

Genetics of progressive supranuclear palsy in a Chinese population.

BACKGROUND: Genetics plays an important role in progressive supranuclear palsy (PSP) and remains poorly understood. A detailed literature search identified 19 PSP-associated genes: MAPT, LRRK2, LRP10, DCTN1, GRN, NPC1, PARK, TARDBP, TBK1, BSN, GBA, STX6, EIF2AK3, MOBP, DUSP10, SLCO1A2, RUNX2, CXCR4, and APOE. To date, genetic studies on PSP have focused on Caucasian population. The gaps in PSP genetic study on East Asian populations need to be filled. METHODS: Exon and flanking regions of the PSP-associated genes were sequenced in 104 patients with PSP and 488 healthy controls. Common variant-based association analysis and gene-based association tests of rare variants were performed using PLINK 1.9 and the sequence kernel association test-optimal, respectively. Additionally, the association of APOE and MAPT genotypes with PSP was evaluated. The above association analyses were repeated among probable PSP patients. Finally, PLINK 1.9 was used to test variants associated with the onset age of PSP. RESULTS: A rare non-pathogenic variant of MAPT (c.425C > T,p.A142V) was detected in a PSP patient. No common variants were significantly associated with PSP. In both the rare-variant and the rare-damaging-variant groups, the combined effect for GBA reached statistical significance (p = 1.43 × 10-3, p = 4.98 × 10-4). The result between APOE, MAPT genotypes and PSP risk were inconsistent across all PSP group and probably PSP group. CONCLUSIONS: The pathogenic variant in MAPT were uncommon in PSP patients. Moreover, GBA gene was likely to increase the risk of PSP, and GBA-associated diseases were beyond α-synucleinopathies. The association between APOE, MAPT and PSP is still unclear among the non-Caucasian population.

Generation of entanglement between a highly wave-packet-tunable photon and a spin-wave memory in cold atoms.

Controls of waveforms (pulse durations) of single photons are important tasks for effectively interconnecting disparate atomic memories in hybrid quantum networks. So far, the waveform control of a single photon that is entangled with an atomic memory remains unexplored. Here, we demonstrated control of waveform length of the photon that is entangled with an atomic spin-wave memory by varying light-atom interaction time in cold atoms. The Bell parameter S as a function of the duration of photon pulse is measured, which shows that violations of Bell inequality can be achieved for the photon pulse in the duration range from 40 ns to 50 µs, where, S = 2.64 ± 0.02 and S = 2.26 ± 0.05 for the 40-ns and 50-µs durations, respectively. The measured results show that S parameter decreases with the increase in the pulse duration. We confirm that the increase in photon noise probability per pulse with the pulse-duration is responsible for the S decrease.

Lack of association between LGMN and Alzheimer's disease in the Southern Han Chinese population.

Recently, functional studies have demonstrated that legumain (LGMN) cleaves both amyloid ß-protein precursor and tau, promoting senile plaques and formation of neurofibrillary tangles, which may play a crucial role in the pathogenesis of Alzheimer's disease (AD). However, the genetic role of LGMN in AD has not been clearly elucidated. Here, we used Sanger sequencing to investigate the single independent (single-variant association test) and cumulative (gene-based association test) effects of variants in the LGMN gene as potential susceptibility factors for AD, in a cohort comprising 676 AD cases and 365 elderly controls from the Han population of South China. In single-variant association analysis, none of the common variants in LGMN were statistically significant. In gene-based analysis, the LGMN gene also showed no association with AD. The results of our replication study in the Alzheimer's Disease Neuroimaging Initiative cohort also showed no association between LGMN and AD. These findings suggest that the LGMN gene may not be a critical factor for AD development.

First case report of cerebral folate deficiency caused by a novel mutation of FOLR1 gene in a Chinese patient.

BACKGROUND: Cerebral folate deficiency (CFD) is a neurological disease, hallmarked by remarkable low concentrations of 5-methyltetrahydrofolic acid (5-MTHF) in cerebrospinal fluid (CSF). The primary causes of CFD include the presence of folate receptor (FR) autoantibodies, defects of FR encoding gene FOLR1, mitochondrial diseases and congenital abnormalities in folate metabolism. CASE PRESENTATION: Here we first present a Chinese male CFD patient whose seizure onset at 2 years old with convulsive status epilepticus. Magnetic Resonance Imaging (MRI) revealed the development of encephalomalacia, laminar necrosis in multiple lobes of the brain and cerebellar atrophy. Whole Exome Sequencing (WES) uncovered a homozygous missense variant of c.524G > T (p.C175F) in FOLR1 gene. Further laboratory tests demonstrated the extremely low level of 5-MTHF in the CSF from this patient, which was attributed to cerebral folate transport deficiency. Following the intravenous and oral treatment of calcium folinate, the concentrations of 5-MTHF in CSF were recovered to the normal range and seizure symptoms were relieved as well. CONCLUSIONS: One novel variation of FOLR1 was firstly identified from a Chinese male patient with tonic-clonic seizures, developmental delay, and ataxia. The WES and laboratory results elucidated the etiology of the symptoms. Clinical outcomes were improved by early diagnosis and proper treatment.

Cavity-enhanced and long-lived optical memories for two orthogonal polarizations in cold atoms.

The storage and retrieval efficiency (SRE) and lifetime of optical quantum memories are two key performance indicators for scaling up quantum information processing. Here, we experimentally demonstrate a cavity-enhanced long-lived optical memory for two polarizations in a cold atomic ensemble. Using electromagnetically induced-transparency (EIT) dynamics, we demonstrate the storages of left-circularly and right-circularly polarized signal light pulses in the atoms, respectively. By making the signal and control beams collinearly pass through the atoms and storing the two polarizations of the signal light as two magnetic-field-insensitive spin waves, we achieve a long-lived (3.5 ms) memory. By placing a low-finesse optical ring cavity around the cold atoms, the coupling between the signal light and the atoms is enhanced, which leads to an increase in SRE. The presented cavity-enhanced storage shows that the SRE is ∼30%, corresponding to an intrinsic SRE of ∼45%.

Deterministic generation and partial retrieval of a spin-wave excitation in an atomic ensemble.

In this paper, we report a generation of a spin-wave excitation (SWE) with a near-unity (0.996±0.003) probability in a given time (~730 µ s). Such deterministic generation relies on a feedback scheme with a millisecond quantum memory. The millisecond memory is achieved by maximizing the wavelength of the spin wave and storing the SWE as the magnetic-field-insensitive transition. We then demonstrate partial retrievals of the spin wave by applying a first read pulse whose area is smaller than the value of π. The remained SWE is fully retrieved by a second pulse. Anti-correlation function between the detections in the first and second readouts has been measured, which shows that the partial-retrieval operation on the SWE is in the quantum regime. The presented experiment represents an important step towards the realization of the improved DLCZ quantum repeater protocol proposed in Phys. Rev. A 77, 062301 (2008).

Enhanced-generation of atom-photon entanglement by using FPGA-based feedback protocol.

The enhanced-generation of entanglement between one atomic collective excitation and a single photon (atom-photon) is very important for practical quantum repeaters and quantum networks based on atomic ensembles and linear optics. We present a feedback-loop algorithm based on field programmable gate array (FPGA) to obtain 21.6-fold increase of the generation rate of atom-photon entanglement at the storage time of 51 µs comparing with no feedback protocol. The generation rate of the atom-photon entanglement is ~3190/s (2100/s) for the excitation probability of 1.65% at the storage time of 1 µs (51 µs). The Bell parameter and the fidelity of atom-photon entanglement at the storage time of 1 µs are 2.40 ± 0.02 and 85.5% ± 0.6%, respectively. The detailed FPGA-based feedback-loop algorithm can be flexibly extended to the multiplexing of atom-photon entanglement, which is expected to further increase the generation rate of atom-photon entanglement.

Spatial Multiplexing of Atom-Photon Entanglement Sources using Feedforward Control and Switching Networks.

The light-matter quantum interface that can create quantum correlations or entanglement between a photon and one atomic collective excitation is a fundamental building block for a quantum repeater. The intrinsic limit is that the probability of preparing such nonclassical atom-photon correlations has to be kept low in order to suppress multiexcitation. To enhance this probability without introducing multiexcitation errors, a promising scheme is to apply multimode memories to the interface. Significant progress has been made in temporal, spectral, and spatial multiplexing memories, but the enhanced probability for generating the entangled atom-photon pair has not been experimentally realized. Here, by using six spin-wave-photon entanglement sources, a switching network, and feedforward control, we build a multiplexed light-matter interface and then demonstrate a ∼sixfold (∼fourfold) probability increase in generating entangled atom-photon (photon-photon) pairs. The measured compositive Bell parameter for the multiplexed interface is 2.49±0.03 combined with a memory lifetime of up to ∼51 µs.

The adsorption and mass-transfer process of cationic red X-GRL dye on natural zeolite.

The adsorption behavior of natural zeolite was studied in order to determine the adsorption capacity and mass-transfer process of cationic red X-GRL (C(18)H(21)BrN(6)) onto the adsorbent. The adsorption tests to determine both the uptake capacity and the mass-transfer process at equilibrium were performed under batch conditions, which showed rapid uptake in general for the initial 5 min, corresponding to 92% total removal. The equilibrium adsorption capacity value (q(e,cal)) in pseudo-second-order kinetics was 13.51 mg/g at 293 K and the whole adsorption process was governed by physical adsorption with an endothermic, endothermic spontaneous nature. Adsorption tests indicated that the zeolite has great potential as an alternative low-cost material in the treatment of X-GRL drainage. However, the mass-transfer process to determine the rate-controlling steps showed that both film diffusion and pore diffusion were important in controlling the adsorption rate. The adsorption process was governed by film diffusion while pore diffusion was poor because the X-GRL molecules could not penetrate into the zeolite easily. The X-GRL molecules were only adsorbed on the external surface of the zeolite. Hence, to improve the adsorption capacity of natural zeolite further, modification to expand its micropores is necessary.

Feasibility of Artificial Intelligence Constrained Compressed SENSE Accelerated 3D Isotropic T1 VISTA Sequence For Vessel Wall MR Imaging: Exploring the Potential of Higher Acceleration Factors Compared to Traditional Compressed SENSE.

RATIONALE AND OBJECTIVES: Investigate the feasibility of using deep learning-based accelerated 3D T1-weighted volumetric isotropic turbo spin-echo acquisition (VISTA) for vessel wall magnetic resonance imaging (VW-MRI), compared to traditional Compressed SENSE and optimize acceleration factor (AF) to obtain high-quality clinical images. METHODS: 40 patients with atherosclerotic plaques in the intracranial or carotid artery were prospectively enrolled in our study from October 1, 2022 to October 31, 2023 underwent high-resolution vessel wall imaging on a 3.0 T MR system using variable Compressed SENSE (CS) AFs and reconstructed by an optimized artificial intelligence constrained Compressed SENSE (CS-AI). Images were reconstructed through both traditional CS and optimized CS-AI. Two radiologists qualitatively assessed the image quality scores of CS and CS-AI across different segments and quantitatively evaluated SNR (signal-to-noise ratio) and CNR (contrast-to-noise ratio) metrics. Paired t-tests, ANOVA, and Friedman tests analyzed image quality metrics. Written informed consent was obtained from all patients in this study. RESULTS: CS-AI groups demonstrated good image quality scores compared to reference scans until AF up to 12 (P < 0.05). The CS-AI 10 protocol provided the best images in the lumen of both normal and lesion sites (P < 0.05). The plaque SNR was significantly higher in CS-AI groups compared to CS groups until the AF increased to 12 (P < 0.05). CS-AI protocols had higher CNR compared to CS with whichever AF on both pre-and post-contrast T1WI (P < 0.05), The CNR was highest in the CS-AI 10 protocol on pre-contrast T1WI and in CS-AI 12 on post-contrast T1WI (P < 0.05). CONCLUSION: The study demonstrated the feasibility of using CS-AI technology to diagnose arteriosclerotic vascular disease with 3D T1 VISTA sequences. The image quality and diagnostic efficiency of CS-AI images were comparable or better than traditional CS images. Higher AFs are feasible and have potential for use in VW-MRI. The determination of standardized AFs for clinical scanning protocol is expected to help for empirical evaluation of new imaging technology.

A Paramagnetic Metal-Organic Framework Enhances Mild Magnetic Hyperthermia Therapy by Downregulating Heat Shock Proteins and Promoting Ferroptosis via Aggravation of Two-Way Regulated Redox Dyshomeostasis.

Mild magnetic hyperthermia therapy (MMHT) holds great potential in treating deep-seated tumors, but its efficacy is impaired by the upregulation of heat shock proteins (HSPs) during the treatment process. Herein, Lac-FcMOF, a lactose derivative (Lac-NH2 ) modified paramagnetic metal-organic framework (FcMOF) with magnetic hyperthermia property and thermal stability, has been developed to enhance MMHT therapeutic efficacy. In vitro studies showed that Lac-FcMOF aggravates two-way regulated redox dyshomeostasis (RDH) via magnetothermal-accelerated ferricenium ions-mediated consumption of glutathione and ferrocene-catalyzed generation of ∙OH to induce oxidative damage and inhibit heat shock protein 70 (HSP70) synthesis, thus significantly enhancing the anti-cancer efficacy of MMHT. Aggravated RDH promotes glutathione peroxidase 4 inactivation and lipid peroxidation to promote ferroptosis, which further synergizes with MMHT. H22-tumor-bearing mice treated with Lac-FcMOF under alternating magnetic field (AMF) demonstrated a 90.4% inhibition of tumor growth. This work therefore provides a new strategy for the simple construction of a magnetic hyperthermia agent that enables efficient MMHT by downregulating HSPs and promoting ferroptosis through the aggravation of two-way regulated RDH.

Compressed Sensitivity Encoding Artificial Intelligence Accelerates Brain Metastasis Imaging by Optimizing Image Quality and Reducing Scan Time.

BACKGROUND AND PURPOSE: Accelerating the image acquisition speed of MR imaging without compromising the image quality is challenging. This study aimed to evaluate the feasibility of contrast-enhanced (CE) 3D T1WI and CE 3D-FLAIR sequences reconstructed with compressed sensitivity encoding artificial intelligence (CS-AI) for detecting brain metastases (BM) and explore the optimal acceleration factor (AF) for clinical BM imaging. MATERIALS AND METHODS: Fifty-one patients with cancer with suspected BM were included. Fifty participants underwent different customized CE 3D-T1WI or CE 3D-FLAIR sequence scans. Compressed SENSE encoding acceleration 6 (CS6), a commercially available standard sequence, was used as the reference standard. Quantitative and qualitative methods were used to evaluate image quality. The SNR and contrast-to-noise ratio (CNR) were calculated, and qualitative evaluations were independently conducted by 2 neuroradiologists. After exploring the optimal AF, sample images were obtained from 1 patient by using both optimized sequences. RESULTS: Quantitatively, the CNR of the CS-AI protocol for CE 3D-T1WI and CE 3D-FLAIR sequences was superior to that of the CS protocol under the same AF (P < .05). Compared with reference CS6, the CS-AI groups had higher CNR values (all P < .05), with the CS-AI10 scan having the highest value. The SNR of the CS-AI group was better than that of the reference for both CE 3D-T1WI and CE 3D-FLAIR sequences (all P < .05). Qualitatively, the CS-AI protocol produced higher image quality scores than did the CS protocol with the same AF (all P < .05). In contrast to the reference CS6, the CS-AI group showed good image quality scores until an AF of up to 10 (all P < .05). The CS-AI10 scan provided the optimal images, improving the delineation of normal gray-white matter boundaries and lesion areas (P < .05). Compared with the reference, CS-AI10 showed reductions in scan time of 39.25% and 39.93% for CE 3D-T1WI and CE 3D-FLAIR sequences, respectively. CONCLUSIONS: CE 3D-T1WI and CE 3D-FLAIR sequences reconstructed with CS-AI for the detection of BM may provide a more effective alternative reconstruction approach than CS. CS-AI10 is suitable for clinical applications, providing optimal image quality and a shortened scan time.

Ultrasonography-based radiomics and computer-aided diagnosis in thyroid nodule management: performance comparison and clinical strategy optimization.

Objectives: To compare ultrasonography (US) feature-based radiomics and computer-aided diagnosis (CAD) models for predicting malignancy in thyroid nodules, and to evaluate their utility for thyroid nodule management. Methods: This prospective study included 262 thyroid nodules obtained between January 2022 and June 2022. All nodules previously underwent standardized US image acquisition, and the nature of the nodules was confirmed by the pathological results. The CAD model exploited two vertical US images of the thyroid nodule to differentiate the lesions. The least absolute shrinkage and operator algorithm (LASSO) was applied to choose radiomics features with excellent predictive properties for building a radiomics model. Ultimately, the area under the receiver operating characteristic curve (AUC) and calibration curves were assessed to compare diagnostic performance between the models. DeLong's test was used to analyze the difference between groups. Both models were used to revise the American College of Radiology Thyroid Imaging Reporting and Data Systems (ACR TI-RADS) to provide biopsy recommendations, and their performance was compared with the original recommendations. Results: Of the 262 thyroid nodules, 157 were malignant, and the remaining 105 were benign. The diagnostic performance of radiomics, CAD, and ACR TI-RADS models had an AUC of 0.915 (95% confidence interval (CI): 0.881-0.947), 0.814 (95% CI: 0.766-0.863), and 0.849 (95% CI: 0.804-0.894), respectively. DeLong's test showed a statistically significant between the AUC values of models (p < 0.05). Calibration curves showed good agreement in each model. When both models were applied to revise the ACR TI-RADS, our recommendations significantly improved the performance. The revised recommendations based on radiomics and CAD showed an increased sensitivity, accuracy, positive predictive value, and negative predictive value, and decreased unnecessary fine-needle aspiration rates. Furthermore, the radiomics model's improvement scale was more pronounced (33.3-16.7% vs. 33.3-9.7%). Conclusion: The radiomics strategy and CAD system showed good diagnostic performance for discriminating thyroid nodules and could be used to optimize the ACR TI-RADS recommendation, which successfully reduces unnecessary biopsies, especially in the radiomics model.

Clinical effect and safety analysis of long-round needle usage in treating cervical spondylotic radiotelegraphy and its effect on pain and functional recovery.

BACKGROUND: Long-round needle usage can treat muscular pain, but there is little research on cervical spondylotic radiculopathy (CSR). OBJECTIVE: To explore the efficacy and safety of long-round needle usage in treating CSR. METHODS: Ninety-eight patients with CSR were randomly divided into control and observation groups. They were treated with filiform needles and long-round needles, respectively. The therapeutic effect, safety, inflammatory factors and neck dysfunction index (NDI), McGill pain questionnaire (MPQ) and Generic Quality of Life Inventory-74 (GQOL-74) scores were compared between the two groups. RESULTS: After treatment, the effective rate and safety of the observation group were better than those of the control group. The NDI and MPQ scores in the observation group were significantly lower than those in the control group, and the GQOL-74 score was higher than that in the control group. The level of interleukin-8 in the observation group was significantly lower than that in the control group, and the level of interleukin-10 was significantly higher than that in the control group. CONCLUSIONS: Long-round needle therapy has a good effect on patients with CSR, which can safely improve the quality of life of patients with mild local inflammatory damage.

Clinical features of progressive supranuclear palsy.

Background: Progressive supranuclear palsy (PSP) is a clinically heterogenous atypical parkinsonian syndrome. Therefore, early recognition and correct diagnosis of PSP is challenging but essential. This study aims to characterize the clinical manifestations, magnetic resonance imaging (MRI), and longitudinal MRI changes of PSP in China. Method: Clinical and MRI presentations were compared among 150 cases with PSP. Then the longitudinal MRI changes among 20 patients with PSP were further explored. Additionally, a series of midbrain-based MRI parameters was compared between PSP-P and PD. Results: Throughout the course of the disease, there were differences in the symptoms of the fall and hand tremor between the PSP-RS and PSP-P. There were significant differences in the six midbrain-based MRI parameters between the PSP-RS and the PSP-P, including hummingbird sign, midbrain diameter, midbrain to pons ratio (MTPR), midbrain area, midbrain area to pons area ratio (Ma/Pa), and midbrain tegmental length (MBTegm). Longitudinal MRI studies revealed that the annual rel.ΔMTPR and rel.Δ (Ma/Pa) for PSP were 5.55 and 6.52%, respectively; additionally, PSP-RS presented a higher decline rate than PSP-P. Moreover, MTPR ≤0.56, midbrain diameter ≤ 0.92, midbrain area ≤ 1.00, and third ventricle width ≤ 0.75 could identify PSP-P from PD. Conclusion: PSP-P differs from PSP-RS regarding clinical manifestations, MRI, and longitudinal MRI changes. MRI parameters could be potential imaging markers to identify PSP-P from PD.

The Application of Deep Brain Stimulation for Progressive Supranuclear Palsy: A Systematic Review.

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease, and currently no effective symptomatic or neuroprotective treatment is available for PSP. Deep brain stimulation (DBS), as a neurosurgical procedure, plays a role in a range of neurological and psychiatric disorders, and a series of case reports have applied DBS in PSP patients. However, there are no systematic investigations about the application of DBS in PSP patients; we therefore performed a systematic review to evaluate the efficacy of DBS for PSP. PubMed, EMBASE and the Cochrane library were systematically searched from database inception to July 31, 2021. Additionally, the reference lists of included studies were searched manually. Of 155 identified studies, 14 were eligible and were included in our analysis (N = 39 participants). We assessed the data between DBS-OFF and DBS-ON conditions, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) and other clinical rating scales. A reduction of UPDRS III scores under DBS-ON conditions in most PSP cases was observed, but the differences yielded no statistical significance. There was no sufficient evidence proving DBS was effective for PSP patients, though part of PSP cases could benefit from DBS and our findings could provide up-to-date information about the possible role of DBS in PSP, which would provide design strategies for following clinical trials and might ultimately help to promote the clinical application of DBS in PSP patients.

Pillar[5]arene based glyco-targeting nitric oxide nanogenerator for hyperthermia-induced triple-mode cancer therapy.

Nitric oxide (NO)-mediated gas therapy (GT) and alkyl radical (R•) therapy (ART) are emerging cancer therapy modes, and multi-mode therapy has been recognized as an attractive strategy for enhancing anti-cancer efficacy. In this work, a thermal-responsive R• initiator 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIBI)-loaded glycol-targeting NO nanogenerator was constructed by first the covalent conjugation of thermal-responsive NO donor of S-nitrosothiols (RSNO) on the surface of mesoporous silica-coated gold nanorods (AuNRs@MSN), then the coating of a supramolecular complex of amino pillar[5]arene (NP5) and galactose derivative (G), and finally the loading of AIBI. The glycol-targeting NO nanogenerator demonstrated specific targeting ability to HepG2 cells owing to the recognition between galactose residues and asialoglycoprotein receptors (ASGPR). Specially, upon 808 nm near-infrared (NIR) irradiation, the AIBI-loaded NO nanogenerator generated hyperthermia to achieve photothermal therapy (PTT), and further GT and ART resulted from the thermal responsiveness of RSNO and AIBI, respectively. In vitro experiments revealed that the AIBI-loaded glyco-targeting NO nanogenerator had good biocompatibility and exhibited effective inhibition to the proliferation of HepG2 cells. This work provides a novel way to supramolecular hybrid drug delivery systems for triple-mode targeting therapy of PTT/GT/ART.

Mutations in GBA, SNCA, and VPS35 are not associated with Alzheimer's disease in a Chinese population: a case-control study.

SNCA, GBA, and VPS35 are three common genes associated with Parkinson's disease. Previous studies have shown that these three genes may be associated with Alzheimer's disease (AD). However, it is unclear whether these genes increase the risk of AD in Chinese populations. In this study, we used a targeted gene sequencing panel to screen all the exon regions and the nearby sequences of GBA, SNCA, and VPS35 in a cohort including 721 AD patients and 365 healthy controls from China. The results revealed that neither common variants nor rare variants of these three genes were associated with AD in a Chinese population. These findings suggest that the mutations in GBA, SNCA, and VPS35 are not likely to play an important role in the genetic susceptibility to AD in Chinese populations. The study was approved by the Ethics Committee of Xiangya Hospital, Central South University, China on March 9, 2016 (approval No. 201603198).

Genetics of Progressive Supranuclear Palsy: A Review.

Progressive supranuclear palsy (PSP) is an atypical parkinsonism with prominent 4R-tau neuropathology, and the classical clinical phenotype is characterized by vertical supranuclear gaze palsy, unprovoked falls, akinetic-rigid syndrome and cognitive decline. Though PSP is generally regarded as sporadic, there is increasing evidence suggesting that a series of common and rare genetic variants impact on sporadic and familial forms of PSP. To date, more than 10 genes have been reported to show a potential association with PSP. Among these genes, the microtubule-associated protein tau (MAPT) is the risk locus with the strongest effect size on sporadic PSP in the case-control genome-wide association studies (GWAS). Additionally, MAPT mutations are the most common cause of familial PSP while the leucine-rich repeat kinase 2 (LRRK2) is a rare monogenic cause of PSP, and several other gene mutations may mimic the PSP phenotype, like the dynactin subunit 1 (DCTN1). In total, 15 MAPT mutations have been identified in cases with PSP, and the mean age at onset is much earlier than in cases carrying LRRK2 or DCTN1 mutations. GWAS have further identified several risk loci of PSP, proposing molecular pathways related to PSP. The present review focused on genetic studies on PSP and summarized genetic factors of PSP, which may help to elucidate the underlying pathogenesis and provide new perspectives for therapeutic strategies.