Synaptic dysfunction plays an important role in the early stage of frontotemporal dementia (FTD), and there are differences in the pattern of synaptic damage in different genotypes. GRN gene mutations are rare in the Chinese population, and there are no reports of synaptic damage patterns in GRN mutations or semantic variant primary progressive aphasia (svPPA). The synaptic injury characteristics of a patient with svPPA harboring GRN gene mutations, which was characterized by decreased synaptic density in the left frontal, temporal, parietal lobe and contralateral cerebellum were reported in this article. The underlying mechanism of synaptic dysfunction involved in the disease process, and potential targets for future clinical interventions were indicated.

Multiple system atrophy(MSA)is a rapidly progressive neurodegenerative disease and, along with Parkinson's disease(PD)and dementia with Lewy bodies(DLB), belongs to the group of α-synucleinopathies.Due to an overlap of clinical symptoms of similar diseases in the early stages and a lack of sensitivity of the current diagnostic criteria to detect the disease in the early stages, difficulties abound in conducting clinical trials on disease-modifying therapeutic agents for its early treatment, and progress in the development of disease-modifying therapeutic agents as well as the development and validation of diagnostic tools has been slow.Consequently, the International Movement Disorder Society(MDS)has introduced new diagnostic criteria for MSA, which, for the first time, propose a category known as possible prodromal MSA and its diagnostic criteria.This review described the diagnostic criteria for possible prodromal MSA and its differential diagnosis from other prodromal α-synucleinopathies, in order to improve the accuracy of diagnosis in the early stages and to promote research on the early stages of the disease.

GBA1 is one of the common risk genes of Parkinson′s disease (PD), which encodes glucocerebrosidase. It is difficult to distinguish PD patients with heterozygous variants of GBA1 ( GBA1-PD) from idiopathic Parkinson′s disease patients, but GBA1-PD tends to progress faster, be more severe, and be more likely to be associated with cognitive impairment and other non-motor symptoms. The pathological mechanism of the increased risk of PD in GBA1 heterozygous variant carriers may be related to autophagy-lysosome dysfunction and mitochondrial dysfunction. Targeted therapy for GBA1 is expected to become a new direction of precision therapy for PD. In this article, the epidemiology and clinical features of GBA1-PD, the possible pathogenesis of GBA1 variation, and the therapeutic strategies for GBA1-PD were elaborated.

Parkinson′s disease (PD) is a common aging-related neurodegenerative disease of the central nervous system. Its pathogenesis is a series of pathophysiological changes under the interaction of genetic factors and environmental risk factors. Recent studies have shown that the pathophysiologic mechanisms outside the central nervous system, especially inflammation and immune response, may play an important role in the pathogenesis of Parkinson′s disease. This article aims to review the up-to-date research results of the peripheral origin of PD, and to discuss the interplay and activation of the peripheral inflammatory immune system in PD.

Gallic Acid/pharmacology* ; Humans ; Senotherapeutics ; Stem Cells

Animals ; Chloroquine/pharmacology* ; Longevity ; Rats

Parkinson′s disease (PD) is the second most common neurodegenerative disease following Alzheimer′s disease. The non-motor symptoms of PD have attracted increasing attention. The occurrence of abnormal blood pressure is related to many factors, including aging, PD related autonomic nerve dysfunction, and drugs for PD treatment,including levodopa, dopamine receptor agonists. Abnormal blood pressure severely limits the clinical use of anti-PD drugs. In order to better understand the relationship between anti-PD drugs and blood pressure in patients with PD. This article summarizes the manifestations of abnormal blood pressure, and analyzes the correlation between anti-PD drugs and blood pressure, summarizes the possible mechanisms of how anti-PD drugs affects the blood pressure in PD.

The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.

Aging/metabolism* ; Animals ; Gene Expression Regulation ; Macaca fascicularis ; Retina/metabolism* ; Single-Cell Analysis