Brain vascular dysfunction in Alzheimer s disease(AD) pathogenesis has become increasingly clea r.Accumulating evidence shows that damaged vascular,including large or small vessels and even neurovascular unit,may acce...Brain vascular dysfunction in Alzheimer s disease(AD) pathogenesis has become increasingly clea r.Accumulating evidence shows that damaged vascular,including large or small vessels and even neurovascular unit,may accelerate the neuropathological process of AD via disrupting brain hypoperfusion,aberrant angiogenesis,and neuroinflammatory response,etc.Thus,vascular dysfunction makes a substantially contribution to the cognitive decline of AD patients.展开更多
In the article titled“Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease”published on pages 2467-2479,Issue 11,Volum...In the article titled“Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease”published on pages 2467-2479,Issue 11,Volume 19 of Neural Regeneration Research(Tang et al.,2024),there are some errors in selecting the appropriate images in Figure 7 by authors during assembling the images.展开更多
Introduction:Spanning the three stages of the Alzheimer’s disease (AD) continuum,amyloid-beta(Aβ40and Aβ42) oligomers (AβO’s) and tau protein constitute a set of biomarkers ideally suited for the non-invasive mon...Introduction:Spanning the three stages of the Alzheimer’s disease (AD) continuum,amyloid-beta(Aβ40and Aβ42) oligomers (AβO’s) and tau protein constitute a set of biomarkers ideally suited for the non-invasive monitoring of AD (Wolgin et al.,2022).AD progression is correlated with the presence of low molecular weight oligomers and not amyloid plaques.Moreover,low molecular weight AβO is present in the beginning and later stages of disease even when the plaque burden becomes prevalent.Furthermore.展开更多
Formation and deposition of amyloid-beta(Aβ) are considered one of the main drivers of Alzheimer's disease(AD). For more than 30 years, Aβ has challenged researchers through its complex physicochemical propertie...Formation and deposition of amyloid-beta(Aβ) are considered one of the main drivers of Alzheimer's disease(AD). For more than 30 years, Aβ has challenged researchers through its complex physicochemical properties and multiple peptide processing steps that involve several proteases(Andreasson et al., 2007).展开更多
Alzheimer’s disease(AD) is the most prevalent neurodegenerative disorder. The major pathological changes in AD progression are the generation and accumulation of amyloid-beta(Aβ) peptides as well as the presence of ...Alzheimer’s disease(AD) is the most prevalent neurodegenerative disorder. The major pathological changes in AD progression are the generation and accumulation of amyloid-beta(Aβ) peptides as well as the presence of abnormally hyperphosphorylated tau proteins in the brain. Autophagy is a conserved degradation pathway that eliminates abnormal protein aggregates and damaged organelles. Previous studies have suggested that autophagy plays a key role in the production and clearance of Aβ peptides to maintain a steady-state of Aβ peptides levels.However, a growing body of evidence suggests that autophagy is significantly impaired in the pathogenesis of AD, especially in Aβ metabolism. Therefore, this article reviews the latest studies concerning the mechanisms of autophagy, the metabolism of Aβ peptides, and the defective autophagy in the production and clearance of Aβpeptides. Here, we also summarize the established and new strategies for targeting autophagy in vivo and through clinical AD trials to identify gaps in our knowledge and to generate further questions.展开更多
The amyloid—what peptide can resist its entropic bliss?Without kinetic barricades and chaperones,most peptides would simply tumble down that precipice.The amyloid-β(Aβ) peptides are understood to underlie the hallm...The amyloid—what peptide can resist its entropic bliss?Without kinetic barricades and chaperones,most peptides would simply tumble down that precipice.The amyloid-β(Aβ) peptides are understood to underlie the hallmark pathology of Alzheimer's disease(AD) and are considered one of the causative factors for neurodegeneration and cognitive impairment.AD affects critical connected structures within the brain that are responsible for memory,language,and social behavior.展开更多
Transmission of misfolded amyloid-β(Aβ)aggregates between human subjects:Protein misfolding disorders are a family of diseases characterized by the accumulation of misfolded protein aggregates.These proteinaceous st...Transmission of misfolded amyloid-β(Aβ)aggregates between human subjects:Protein misfolding disorders are a family of diseases characterized by the accumulation of misfolded protein aggregates.These proteinaceous structures,also known as amyloids,are key drivers of fatal neurodegenerative disorders such as prion diseases,Alzheimer’s disease(AD),Parkinson’s disease,and others.展开更多
Compelling evidence demonstrates that the levels of peripheral amyloid-β(Aβ)fluctuate in Alzheimer’s disease(AD)patients.Moreover,Aβdeposits have been identified in peripheral tissues.However,the relevance of peri...Compelling evidence demonstrates that the levels of peripheral amyloid-β(Aβ)fluctuate in Alzheimer’s disease(AD)patients.Moreover,Aβdeposits have been identified in peripheral tissues.However,the relevance of peripheral Aβ(misfolded or not)in pathological situations,and the temporal appearance of these pathological fluctuations,are not well understood.The presence of misfolded Aβin peripheral compartments raises concerns on potential inter-individual transmissions considering the well-reported prion-like properties of this disease-associated protein.The latter is supported by multiple reports demonstrating that Aβmisfolding can be transmitted between humans and experimental animals through multiple routes of exposure.In this mini-review,we discuss the potential implications of peripheral,disease-associated Aβin disease mechanisms,as well as in diagnostic and therapeutic approaches.展开更多
Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event cau...Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the pathology.However,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one another.Some researchers argue that these proteins are mere executors rather than primary causes of pathology.Therefore,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early AD.Moreover,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).展开更多
The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as amyloidosis.Transthyretin(TTR)is one of the>30 amyloidogenic prote...The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as amyloidosis.Transthyretin(TTR)is one of the>30 amyloidogenic proteins identified to date and is associated with a group of highly debilitating and life-threatening disorders called TTR amyloidosis(ATTR).ATTR comprises senile systemic amyloidosis,which is linked to wild-type(WT)TTR aggregation,and hereditary ATTR,a dominantly inherited disorder caused by the deposition of one of over 130 TTR genetic variants.Senile systemic amyloidosis is a prevalent age-related amyloidosis,affecting up to 25%of the population over 80 years of age,and is characterized by the build-up of TTR fibrils in the myocardium.Regarding hereditary ATTR,the clinical presentation is highly heterogeneous,primarily affecting the peripheral nervous system(familial amyloid polyneuropathy-FAP)or the heart(familial amyloid cardiomyopathy).In rare cases,aggregation develops in the central nervous system,giving rise to a phenotype known as familial leptomeningeal amyloidosis(Carroll et al.,2022).展开更多
Ce-encapsulated Beta zeolite was synthesized by a one-pot hydrothermal method with citric acid complexing Ce in the absence of Na species.Additional citric acid can effectively prevent the deposition of Ce species dur...Ce-encapsulated Beta zeolite was synthesized by a one-pot hydrothermal method with citric acid complexing Ce in the absence of Na species.Additional citric acid can effectively prevent the deposition of Ce species during the hydrothermal synthesis of zeolites,leading to uniform distribution of Ce cluster in the framework of Beta zeolites.Moreover,the sodium-free synthesis system resulted that the Brønsted acid sites were mainly located on the straight channels and external surface of Beta zeolites,improving the utilization of Brønsted acid sites.In addition,Ce encapsulated Beta zeolites showed enhanced activity and robust stability in the alkylation of benzene with 1-dodecene based on the synergistic effect between Ce species and Brønsted acid sites,which pave the way for its practical application in the production of alkylbenzene.展开更多
This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral ang...This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral angiography-MRI revealed features indicative of CAA. Symptomatic treatment resulted in improvement, but the patient later developed a fatal hematoma. The discussion navigates the intricate therapeutic landscape of repetitive TIAs in the elderly with cardiovascular risk factors, emphasizing the pivotal role of cerebral MRI and meticulous bleeding risk management. The conclusion stresses the importance of incorporating SWI sequences, specifically when suspecting a cardioembolic TIA, as a diagnostic measure to explore and exclude CAA in the differential diagnosis. This case report provides valuable insights into these challenges, highlighting the need to consider CAA in relevant cases.展开更多
Beta diversity,the variation of community composition among sites,bridges alpha and gamma diversity and can reveal the mechanisms of community assembly through applying distance-decay models and/or partitioning beta d...Beta diversity,the variation of community composition among sites,bridges alpha and gamma diversity and can reveal the mechanisms of community assembly through applying distance-decay models and/or partitioning beta diversity into turnover and nestedness components from functional and phylogenetic perspectives.Mountains as the most natural experiment system provide good opportunities for exploring beta diversity patterns and the underlying ecological processes.Here,we simultaneously consider distance-decay models and multiple di-mensions of beta diversity to examine spatial variations of bird communities,and to evaluate the relative importance of niche-based and neutral community assembly mechanisms along a 3600-m elevational gradient in the central Himalayas,China.Our results showed that species turnover dominates taxonomic,functional,and phylogenetic beta diversity.We observed strongest evidence of spatial distance decays in taxonomic similarities of birds,followed by its phylogenetic and functional analogues.Turnover component was highest in taxonomic beta diversity,while nestedness component was highest in functional beta diversity.Further,all correlations of assemblage similarity with climatic distance were higher than that with spatial distances.Standardized values of overall taxonomic,functional,and phylogenetic beta diversity and their turnover components increase with increasing elevational distance,while the standardized values of taxonomic and phylogenetic nestedness decreased with increasing elevational distance.Our results highlighted the niche-based deterministic processes in shaping elevational bird diversity patterns that were determined by the relative roles of decreasing trend of environmental filtering and increasing trend of limiting similarity along elevation distances.展开更多
基金supported by the Science and Technology Innovation 2030-Major Projects,No.2022ZD021 1 600the National Natural Science Foundation of China,Nos.82271574 and82071204 (all to CX)。
文摘Brain vascular dysfunction in Alzheimer s disease(AD) pathogenesis has become increasingly clea r.Accumulating evidence shows that damaged vascular,including large or small vessels and even neurovascular unit,may accelerate the neuropathological process of AD via disrupting brain hypoperfusion,aberrant angiogenesis,and neuroinflammatory response,etc.Thus,vascular dysfunction makes a substantially contribution to the cognitive decline of AD patients.
文摘In the article titled“Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease”published on pages 2467-2479,Issue 11,Volume 19 of Neural Regeneration Research(Tang et al.,2024),there are some errors in selecting the appropriate images in Figure 7 by authors during assembling the images.
基金National Research Foundation of Korea (NRF) by the Korean Government (2020R1A2B5B01002463&2021R1A6A1A03038996)(to JPH)。
文摘Introduction:Spanning the three stages of the Alzheimer’s disease (AD) continuum,amyloid-beta(Aβ40and Aβ42) oligomers (AβO’s) and tau protein constitute a set of biomarkers ideally suited for the non-invasive monitoring of AD (Wolgin et al.,2022).AD progression is correlated with the presence of low molecular weight oligomers and not amyloid plaques.Moreover,low molecular weight AβO is present in the beginning and later stages of disease even when the plaque burden becomes prevalent.Furthermore.
基金Ministerium für Wissenschaft und Gesundheit (MWG),Rheinland Pfalz,Neurodeg X Forschungskolleg (to BB)。
文摘Formation and deposition of amyloid-beta(Aβ) are considered one of the main drivers of Alzheimer's disease(AD). For more than 30 years, Aβ has challenged researchers through its complex physicochemical properties and multiple peptide processing steps that involve several proteases(Andreasson et al., 2007).
基金supported by the Construction Project of Capacity Improvement Plan for Chongqing Municipal Health Commission affiliated unit (2019NLTS001)-ZS03174operating grant to Chongqing Key Laboratory of Neurodegenerative Diseases (Grant No. 1000013)+2 种基金Chongqing Talent Project [2000062]Overseas Students entrepreneurial fund (Grant No. 2000079)Plan for High-level Talent Introduction (Grant No. 2000055)。
文摘Alzheimer’s disease(AD) is the most prevalent neurodegenerative disorder. The major pathological changes in AD progression are the generation and accumulation of amyloid-beta(Aβ) peptides as well as the presence of abnormally hyperphosphorylated tau proteins in the brain. Autophagy is a conserved degradation pathway that eliminates abnormal protein aggregates and damaged organelles. Previous studies have suggested that autophagy plays a key role in the production and clearance of Aβ peptides to maintain a steady-state of Aβ peptides levels.However, a growing body of evidence suggests that autophagy is significantly impaired in the pathogenesis of AD, especially in Aβ metabolism. Therefore, this article reviews the latest studies concerning the mechanisms of autophagy, the metabolism of Aβ peptides, and the defective autophagy in the production and clearance of Aβpeptides. Here, we also summarize the established and new strategies for targeting autophagy in vivo and through clinical AD trials to identify gaps in our knowledge and to generate further questions.
基金supported by the National Institutes of Health Grant (R01-AG062469)the Grantin-Aid of Research,Artistry,Scholarship program (GIA,Project 143977) at the University of Minnesotafunding from the Center for Drug Design (CDD),University of Minnesota (to SSM)。
文摘The amyloid—what peptide can resist its entropic bliss?Without kinetic barricades and chaperones,most peptides would simply tumble down that precipice.The amyloid-β(Aβ) peptides are understood to underlie the hallmark pathology of Alzheimer's disease(AD) and are considered one of the causative factors for neurodegeneration and cognitive impairment.AD affects critical connected structures within the brain that are responsible for memory,language,and social behavior.
基金supported by grants from the Alzheimer’s Association(AARGD-18-566576)NIH/NIA(RF1AG072491)NIH/NIAID(R01AI132695)to RM。
文摘Transmission of misfolded amyloid-β(Aβ)aggregates between human subjects:Protein misfolding disorders are a family of diseases characterized by the accumulation of misfolded protein aggregates.These proteinaceous structures,also known as amyloids,are key drivers of fatal neurodegenerative disorders such as prion diseases,Alzheimer’s disease(AD),Parkinson’s disease,and others.
基金supported by grants from NIH(RF1AG072491 and R01AI132695)to RM.
文摘Compelling evidence demonstrates that the levels of peripheral amyloid-β(Aβ)fluctuate in Alzheimer’s disease(AD)patients.Moreover,Aβdeposits have been identified in peripheral tissues.However,the relevance of peripheral Aβ(misfolded or not)in pathological situations,and the temporal appearance of these pathological fluctuations,are not well understood.The presence of misfolded Aβin peripheral compartments raises concerns on potential inter-individual transmissions considering the well-reported prion-like properties of this disease-associated protein.The latter is supported by multiple reports demonstrating that Aβmisfolding can be transmitted between humans and experimental animals through multiple routes of exposure.In this mini-review,we discuss the potential implications of peripheral,disease-associated Aβin disease mechanisms,as well as in diagnostic and therapeutic approaches.
基金supported by grants PID2020-115823-GB100 funded by MCIN/AEI/10.13039/501100011033SBPLY/21/180501/000150 funded by JCCM/ERDF-A way of making Europe+1 种基金2022-GRIN-34354 grant by UCLM/ERDF intramural funding to LJDJDNL.DJ held a predoctoral fellowship granted by UCLM/ESF“Plan Propio de Investigación.”。
文摘Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the pathology.However,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one another.Some researchers argue that these proteins are mere executors rather than primary causes of pathology.Therefore,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early AD.Moreover,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).
基金funded by the Spanish Ministry of Science and Innovation(PDC2021-120914-I00)the Universitat Autònoma de Barcelona(PROOF OF CONCEPT 2020)ICREA,ICREA-Academia 2015 and 2020(to SV).
文摘The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as amyloidosis.Transthyretin(TTR)is one of the>30 amyloidogenic proteins identified to date and is associated with a group of highly debilitating and life-threatening disorders called TTR amyloidosis(ATTR).ATTR comprises senile systemic amyloidosis,which is linked to wild-type(WT)TTR aggregation,and hereditary ATTR,a dominantly inherited disorder caused by the deposition of one of over 130 TTR genetic variants.Senile systemic amyloidosis is a prevalent age-related amyloidosis,affecting up to 25%of the population over 80 years of age,and is characterized by the build-up of TTR fibrils in the myocardium.Regarding hereditary ATTR,the clinical presentation is highly heterogeneous,primarily affecting the peripheral nervous system(familial amyloid polyneuropathy-FAP)or the heart(familial amyloid cardiomyopathy).In rare cases,aggregation develops in the central nervous system,giving rise to a phenotype known as familial leptomeningeal amyloidosis(Carroll et al.,2022).
基金supported by the National Natural Science Foundation of China(22278090,21978055)Natural Science Foundation of Guangdong Province,China(2022A1515012088)the Science and Technology Planning Project of Guangdong Province,China(2022A0505030073,2022A0505030013).
文摘Ce-encapsulated Beta zeolite was synthesized by a one-pot hydrothermal method with citric acid complexing Ce in the absence of Na species.Additional citric acid can effectively prevent the deposition of Ce species during the hydrothermal synthesis of zeolites,leading to uniform distribution of Ce cluster in the framework of Beta zeolites.Moreover,the sodium-free synthesis system resulted that the Brønsted acid sites were mainly located on the straight channels and external surface of Beta zeolites,improving the utilization of Brønsted acid sites.In addition,Ce encapsulated Beta zeolites showed enhanced activity and robust stability in the alkylation of benzene with 1-dodecene based on the synergistic effect between Ce species and Brønsted acid sites,which pave the way for its practical application in the production of alkylbenzene.
文摘This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral angiography-MRI revealed features indicative of CAA. Symptomatic treatment resulted in improvement, but the patient later developed a fatal hematoma. The discussion navigates the intricate therapeutic landscape of repetitive TIAs in the elderly with cardiovascular risk factors, emphasizing the pivotal role of cerebral MRI and meticulous bleeding risk management. The conclusion stresses the importance of incorporating SWI sequences, specifically when suspecting a cardioembolic TIA, as a diagnostic measure to explore and exclude CAA in the differential diagnosis. This case report provides valuable insights into these challenges, highlighting the need to consider CAA in relevant cases.
基金supported by the Key R&D Program of Tibet Auton-omous Region(XZ202301ZY0019G)Project for the Local Development of Science and Technology by the Central Government(XZ202301YD0007C)the National Natural Science Foundation of China(No.31400361).
文摘Beta diversity,the variation of community composition among sites,bridges alpha and gamma diversity and can reveal the mechanisms of community assembly through applying distance-decay models and/or partitioning beta diversity into turnover and nestedness components from functional and phylogenetic perspectives.Mountains as the most natural experiment system provide good opportunities for exploring beta diversity patterns and the underlying ecological processes.Here,we simultaneously consider distance-decay models and multiple di-mensions of beta diversity to examine spatial variations of bird communities,and to evaluate the relative importance of niche-based and neutral community assembly mechanisms along a 3600-m elevational gradient in the central Himalayas,China.Our results showed that species turnover dominates taxonomic,functional,and phylogenetic beta diversity.We observed strongest evidence of spatial distance decays in taxonomic similarities of birds,followed by its phylogenetic and functional analogues.Turnover component was highest in taxonomic beta diversity,while nestedness component was highest in functional beta diversity.Further,all correlations of assemblage similarity with climatic distance were higher than that with spatial distances.Standardized values of overall taxonomic,functional,and phylogenetic beta diversity and their turnover components increase with increasing elevational distance,while the standardized values of taxonomic and phylogenetic nestedness decreased with increasing elevational distance.Our results highlighted the niche-based deterministic processes in shaping elevational bird diversity patterns that were determined by the relative roles of decreasing trend of environmental filtering and increasing trend of limiting similarity along elevation distances.
