RNA splicing is an essential cellular process in which a series of protein-nucleic acid complexes cut and splice the products of gene transcription to generate mature RNA， and it plays an important role in maintaining the normal life activities of cells. Extensive studies have shown that proteins and nucleic acids associated with RNA splicing undergo the pathological changes such as aggregation in neurodegenerative diseases， and inadequate RNA splicing is observed in lesions. Genetic alterations within RNA splicing-related genes can cause neurodegenerative diseases. All these findings suggest that abnormalities in RNA splicing pathways may play a significant role in the pathogenesis of neurodegenerative diseases. This article reviews the research advances in the alterations of RNA splicing in common neurodegenerative diseases in terms of histopathology， biochemistry， and genetics， as well as related cell biology and animal models， in order to clarify their role in the pathogenesis of neurodegenerative diseases.
Alzheimer Disease ; Parkinson Disease

Humans ; Alzheimer Disease ; Cross-Sectional Studies ; Creatine Kinase ; Brain/metabolism*

Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.
Humans ; Mice ; Animals ; Transcranial Magnetic Stimulation ; Alzheimer Disease/therapy* ; Cognitive Dysfunction/therapy* ; Cognition ; Sulfur ; Iron ; Iron-Sulfur Proteins ; Mitochondrial Proteins

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, or Amyotrophic Lateral Sclerosis. In a process known as 'seeding', prion-like proteins such as amyloid beta, microtubule-associated protein tau, α-synuclein, silence superoxide dismutase 1, or transactive response DNA-binding protein 43 kDa, propagate their misfolded conformations by transforming their respective soluble monomers into fibrils. Cellular and molecular evidence of prion-like propagation in NDs, the clinical relevance of their 'seeding' capacities, and their levels of contribution towards disease progression have been intensively studied over recent years. This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization, endo-lysosomal leaking, aggregate degradation, and secretion. Debates on the importance of the role of prion-like protein aggregates in NDs, whether causal or consequent, are also discussed. Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.
Humans ; Prions ; Neurodegenerative Diseases/pathology* ; Amyloid beta-Peptides ; Alzheimer Disease ; alpha-Synuclein ; tau Proteins ; Parkinson Disease

Objective To investigate the relationship between neurofilament light chain protein （NfL） and clinical features in patients with Alzheimer disease. Methods We included 58 patients with Alzheimer's disease admitted to Ningbo No. 2 Hospital from June 2020 to December 2021. NfL levels were measured for the 58 patients with Alzheimer's disease. Correlation analysis was performed to study the correlation between NfL and age， disease course， hippocampal grade， Activities of Daily Living（ADL） score， Mini-Mental State Examination （MMSE） score， and Hasegawa Dementia Scale （HDS） score. The Pearson correlation coefficient （r） represented the strength of correlation. Results Among the 58 patients， 33 were females， with a mean NfL level of（24.93±17.07）pg/mL， and 24 were males， with a mean NfL level of 28.14 ± 17.98 pg/mL， which were not significantly different. NfL levels for different educational attainments had no significant difference： illiteracy （7/58），（27.87 ± 14.75）pg/mL；primary school（7/58），（15.22±9.62）pg/mL；middle school （14/58）， （27.95±15.60）pg/mL； high school（4/58），（12.84±2.97）pg/mL； technical secondary school（7/58）， （37.35±26.63）pg/mL； junior college （5/58），（33.79±21.81）pg/mL； and university （7/58），（15.22±9.62）pg/mL. NfL was positively correlated with age （r=0.448） and hippocampal grade（r=0.345）， and not significantly correlated with the course of disease（r=0.045，P>0.05）， ADL score （r=0.242，P>0.05），MMSE score （r=‒0.099，P>0.05），and HDS score （r=‒0.096，P>0.05）. Conclusion Serum NfL levels in patients with Alzheimer disease are positively correlated with age and hippocampal grade on magnetic resonance imaging， but not associated with sex， education attainments， the course of disease，ADL score，MMSE score，and HDS score.
Alzheimer Disease

Previous studies mainly used β-amyloid and α-synuclein as the biomarkers for the diagnosis of neurodegenerative diseases. In recent years，studies have shown that telomeres at the end of chromosome can be used as an index to measure the degree of biological aging，and telomere length and telomerase activity may also be used as the blood markers to evaluate the risk，progression，and poor prognosis of neurodegenerative diseases in the elderly；however，there is still a lack of consistency between the research findings in China and globally. Understanding the role of telomere-related biomarkers in age-related diseases can help clinicians learn more about the mechanism of disease development and progression. This article reviews the latest research advances in the telomere-telomerase system in neurodegenerative diseases，in order to introduce the influence of telomere length and telomerase activity on neurodegenerative diseases and their potential mechanisms of action.
Telomere ; Telomerase ; Neurodegenerative Diseases ; Alzheimer Disease ; Parkinson Disease

Enlarged perivascular spaces（EPVSs）are one of the imaging biomarkers of cerebral small vessel disease（CSVD），and associated with other pathological changes of CSVD，worse cognitive function，and aging. This review describes the imaging characteristics and visual rating of EPVSs using magnetic resonance imaging and summarizes the research progress of EPVSs in Alzheimer disease in recent years in order to promote the understanding of this field.
Alzheimer Disease

Alzheimer disease（AD）， a degenerative disease of the central nervous system characterized by progressive cognitive dysfunction and behavioral impairment， has gradually become one of the most burdensome diseases in this century. At present， the amyloid cascade hypothesis is a widely recognized theory on the pathogenesis of AD. However， recent studies have shown that the immune system can play an important role in the occurrence of AD. This article summarizes the relationship between the immune system and the development and progression of AD from the existing literature， with an emphasis on the role of peripheral immunity in both the innate and adaptive immune systems， aiming to provide novel ideas for future research on AD in the immunological direction.
Alzheimer Disease

Diagnosis of Alzheimer dementia is done clinically using criteria set by different neurological associations. Inevitably, clinicians encounter cases that do not fulfill the set definitions and have to resort to supporting data to form a clinical judgment. Part of the ancillary work-up for dementia is the brain amyloid PET scan that has recently been available in the Philippines. It involves a radiopharmaceutical with high-affinity binding to amyloid plaques which for a time were thought to be central pathological finding for Alzheimer dementia. This study describes the first four amyloid PET scans in the Philippines and detail the protocol as well as interpretation of such studies. The procedure is not as simple and reproducible as one might think hence following the recommended protocol and interpretation guidelines are of utmost importance. We recommend standardization of the reporting of results for all centers that will cater to patients being worked up for dementia, which include reporting SUVRs for both whole cerebellum and cerebellar cortex. More studies are recommended to generate a local Florbetaben SUVR cutoff.
Alzheimer Disease ; Diagnostic Imaging

INTRODUCTION: This study aimed to elucidate the cognitive profile of patients with mild cognitive impairment with Lewy bodies (MCI-LB) and to compare it to that of patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD). METHODS: Subjects older than 60 years with probable MCI-LB (n = 60) or MCI-AD (n = 60) were recruited. All patients were tested with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to assess their global cognitive profile. RESULTS: The MCI-AD and MCI-LB patients did not differ in total MMSE and MoCA scores. However, some sub-items in MMSE and MoCA were shown to be screening markers for differentiating MCI-LB from MCI-AD. In the visuoconstructive test, the total score and hands subitem score in the clock-drawing test were significantly lower in MCI-LB than in MCI-AD. As for the executive function, the 'animal fluency test', 'repeat digits backward test' and 'take paper by your right hand' in MMSE all showed lower scores in MCI-LB compared with MCI-AD. As for memory, 'velvet' and 'church' in MoCA and 'ball' and 'national flag' in MMSE had lower scores in MCI-AD than in MCI-LB. CONCLUSION This study presents the cognitive profile of patients with MCI-LB. In line with the literature on Dementia with Lewy bodies, our results showed lower performance on tests for visuoconstructive and executive function, whereas memory remained relatively spared in the early period.
Humans ; Cognitive Dysfunction ; Alzheimer Disease/diagnosis* ; Neuropsychological Tests ; Cognition