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Background and purpose The insidious onset of Parkinson's disease (PD) makes early diagnosis difficult. Notably, idiopathic rapid eye movement sleep behavior disorder (iRBD) was reported as a prodrome of PD, which may represent a breakthrough for the early diagnosis of PD. However, currently there is no reliable biomarker for PD diagnosis. Considering that α‐synuclein (α‐Syn) and neuroinflammation are known to develop prior to the onset of clinical symptoms in PD, it was hypothesized that plasma total exosomal α‐Syn (t‐exo α‐Syn), neural‐derived exosomal α‐Syn (n‐exo α‐Syn) and exosomal apoptosis‐associated speck‐like protein containing a caspase activation and recruitment domain (ASC) may be potential biomarkers of PD. Methods In this study, 78 PD patients, 153 probable iRBD patients (pRBD) and 63 healthy controls (HCs) were recruited. α‐Syn concentrations were measured using a one‐step paramagnetic particle‐based chemiluminescence immunoassay, and ASC levels were measured using the Ella system. Results It was found that t‐exo α‐Syn was significantly increased in the PD group compared to the pRBD and HC groups (p < 0.0001), whilst n‐exo α‐Syn levels were significantly increased in both the PD and pRBD groups compared to HCs (p < 0.0001). Furthermore, although no difference was found in ASC levels between the PD and pRBD groups, there was a positive correlation between ASC and α‐Syn in exosomes. Conclusions Our results suggest that both t‐exo α‐Syn and n‐exo α‐Syn were elevated in the PD group, whilst only n‐exo α‐Syn was elevated in the pRBD group. Additionally, the adaptor protein of inflammasome ASC is correlated with α‐Syn and may facilitate synucleinopathy.

Alpha-synucleinopathy is postulated to be central to both idiopathic rapid eye movement sleep behaviour disorder (iRBD) and Parkinson’s disease (PD). Growing evidence suggests an association between the diminished clearance of α-synuclein and glymphatic system dysfunction. However, evidence accumulating primarily based on clinical data to support glymphatic system dysfunction in patients with iRBD and PD is currently insufficient. This study aimed to use diffusion tensor image analysis along the perivascular space (DTI-ALPS) to evaluate glymphatic system activity and its relationship to clinical scores of disease severity in patients with possible iRBD (piRBDs) and those with PD. Further, we validated the correlation between the ALPS index and the prognosis of PD longitudinally. Overall, 168 patients with PD, 119 piRBDs, and 129 healthy controls were enroled. Among them, 50 patients with PD had been longitudinally reexamined. Patients with PD exhibited a lower ALPS index than those with piRBDs (P = 0.036), and both patient groups showed a lower ALPS index than healthy controls (P < 0.001 and P = 0.001). The ALPS index and elevated disease severity were negatively correlated in the piRBD and PD subgroups. Moreover, the ALPS index was correlated with cognitive decline in patients with PD in the longitudinal analyses. In conclusion, DTI-ALPS provided neuroimaging evidence of glymphatic system dysfunction in piRBDs and patients with PD; however, the potential of assessing the pathological progress of α-synucleinopathies as an indicator is worth verifying. Further development of imaging methods for glymphatic system function is also warranted.

Aspergillus abscesses in the cerebellum are extremely rare, and most cases are solitary. Here, we report the first case of multiple Aspergillus cerebellar abscesses in a 46-year-old female after one mastoidectomy, two craniectomies, and extended use of antibiotics. The possible pathogenesis of this unusual event is discussed. Good outcome was achieved by treatment with a combination of neurosurgical resection and voriconazole (VRC) administration, which we suggest is a potential management plan.

The brain glymphatic system is involved in the clearance of misfolding α-synuclein, the impaired glymphatic system may contribute to the progression of Parkinson’s disease (PD). We aimed to analyze the diffusion tensor image along the perivascular space (DTI-ALPS) and perivascular space (PVS) burden to reveal the relationship between the glymphatic system and PD. A cross-sectional study using a 7 T MRI of 76 PD patients and 48 controls was performed to evaluate the brain’s glymphatic system. The DTI-ALPS and PVS burden in basal ganglia were calculated. Correlation analyses were conducted between DTI-ALPS, PVS burden and clinical features. We detected lower DTI-ALPS in the PD subgroup relative to controls, and the differences were more pronounced in patients with Hoehn & Yahr stage greater than two. The decreased DTI-ALPS was only evident in the left hemisphere in patients in the early stage but involved both hemispheres in more advanced PD patients. Decreased DTI-ALPS were also correlated with longer disease duration, higher Unified Parkinson’s Disease Rating Scale motor score (UPDRS III) and UPDRS total scores, as well as higher levodopa equivalent daily dose. Moreover, the decreased DTI-ALPS correlated with increased PVS burden, and both indexes correlated with PD disease severity. This study demonstrated decreased DTI-ALPS in PD, which might initiate from the left hemisphere and progressively involve right hemisphere with the disease progression. Decreased DTI-ALPS index correlated with increased PVS burden, indicating that both metrics could provide supporting evidence of an impaired glymphatic system. MRI evaluation of the PVS burden and diffusion along PVS are potential imaging biomarkers for PD for disease progression.

In Parkinson's disease (PD), iron accumulation in the substantia nigra (SN) exacerbates oxidative stress and α-synuclein aggregation, leading to neuronal death. However, the influence of ironrelated nigral degeneration on the subcortical function and global network configuration in PD remains unknown. Ninety PD patients and 38 normal controls underwent clinical assessments and multimodality magnetic resonance imaging scans. Iron accumulation in the inferior SN and disrupted functional connectivity between the bilateral striatums were observed in PD, and negative correlation between them was found in the whole population. The binarized functional *

Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder that destroys cognitive functions. Recently, a number of high-profile clinical trials based on the amyloid cascade hypothesis have encountered disappointing results. The failure of these trials indicates the necessity for novel therapeutic strategies and disease models. In this review, we will describe how recent advances in stem cell technology have shed light on a novel treatment strategy and revolutionized the mechanistic investigation of AD pathogenesis. Current advances in promoting endogenous neurogenesis and transplanting exogenous stem cells from both bench research and clinical translation perspectives will be thoroughly summarized. In addition, reprogramming technology-based disease modeling, which has shown improved efficacy in recapitulating pathological features in human patients, will be discussed.

Heterogeneity between late-onset Parkinson's disease (LOPD) and early-onset Parkinson's disease (EOPD) is mainly reflected in the following aspects including genetics, disease progression, drug response, clinical manifestation, and neuropathological change. Although many studies have investigated these differences in relation to clinical significance, the functional processing circuits and underlying neural mechanisms have not been entirely understood. In this study, regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) maps were used to explore different spontaneous brain activity patterns in EOPD and LOPD patients. Abnormal synchronizations were found in the motor and emotional circuits of the EOPD group, as well as in the motor, emotional, and visual circuits of the LOPD group. EOPD patients showed functional activity change in the visual, emotional and motor circuits, and LOPD patients only showed increased functional activity in the emotional circuits. In summary, the desynchronization process in the LOPD group was relatively strengthened, and the brain areas with changed functional activity in the EOPD group were relatively widespread. The results might point out different impairments in the synchronization and functional activity for EOPD and LOPD patients.