Alzheimer’s disease（AD）is the most common form of dementia representing a major problem for public health.In 2017 there were an estimated 50 million patients worldwide and this number is expected to almost double e...Alzheimer’s disease（AD）is the most common form of dementia representing a major problem for public health.In 2017 there were an estimated 50 million patients worldwide and this number is expected to almost double every 20years,reaching 75 million in 2030 and 131.5 million in 2050（https：//www.alz.co.uk/research/statistics）.展开更多
The regional specifi city of hippocampal abnormalities in late-life depression（LLD） has been demonstrated in previous studies. In this study,we sought to examine the functional connectivity（FC） patterns of hippoca...The regional specifi city of hippocampal abnormalities in late-life depression（LLD） has been demonstrated in previous studies. In this study,we sought to examine the functional connectivity（FC） patterns of hippocampal subregions in remitted late-onset depression（r LOD）,a special subtype of LLD. Fourteen r LOD patients and 18 healthy controls underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging scans at baseline and at ~21 months of follow-up. Each hippocampus was divided into three parts,the cornu ammonis（CA）,the dentate gyrus,and the subicular complex,and then six seed-based hippocampal subregional networks were established.Longitudinal changes of the six networks over time were directly compared between the rL OD and control groups. From baseline to follow-up,the r LOD group showed a greater decline in connectivity of the left CA to the bilateral posterior cingulate cortex/precuneus（PCC/PCUN）,but showed increased connectivity of the right hippocampal subregional networks with the frontal cortex（bilateral medial prefrontal cortex/anterior cingulate cortex and supplementary motor area）. Further correlative analyses revealed thatthe longitudinal changes in FC between the left CA and PCC/PCUN were positively correlated with longitudinal changes in the Symbol Digit Modalities Test（r = 0.624,P = 0.017） and the Digit Span Test（r = 0.545,P = 0.044） scores in the r LOD group. These results may provide insights into the neurobiological mechanism underlying the cognitive dysfunction in r LOD patients.展开更多
The last decades have witnessed huge efforts devoted to deciphering the pathological mechanisms underlying Alzheimer’s Disease(AD)and to testing new drugs,with the recent FDA approval of two anti-amyloid monoclonal a...The last decades have witnessed huge efforts devoted to deciphering the pathological mechanisms underlying Alzheimer’s Disease(AD)and to testing new drugs,with the recent FDA approval of two anti-amyloid monoclonal antibodies for AD treatment.Beyond these drug-based experimentations,a number of pre-clinical and clinical trials are exploring the benefits of alternative treatments,such as non-invasive stimulation techniques on AD neuropathology and symptoms.Among the different non-invasive brain stimulation approaches,transcranial alternating current stimulation(tACS)is gaining particular attention due to its ability to externally control gamma oscillations.Here,we outline the current knowledge concerning the clinical efficacy,safety,ease-of-use and cost-effectiveness of tACS on early and advanced AD,applied specifically at 40 Hz frequency,and also summarise pre-clinical results on validated models of AD and ongoing patient-centred trials.展开更多
Endosomes are crucial sites for intracellular material sorting and transportation.Endosomal transport is a critical process involved in the selective uptake,processing,and intracellular transport of substances.The equ...Endosomes are crucial sites for intracellular material sorting and transportation.Endosomal transport is a critical process involved in the selective uptake,processing,and intracellular transport of substances.The equilibrium between endocytosis and circulation mediated by the endosome-centered transport pathway plays a significant role in cell homeostasis,signal transduction,and immune response.In recent years,there have been hints linking endosomal transport abnormalities to neurodegenerative diseases,including Alzheimer’s disease.Nonetheless,the related mechanisms remain unclear.Here,we provide an overview of endosomal-centered transport pathways and highlight potential physiological processes regulated by these pathways,with a particular focus on the correlation of endosomal trafficking disorders with common pathological features of neurodegenerative diseases.Additionally,we summarize potential therapeutic agents targeting endosomal trafficking for the treatment of neurodegenerative diseases.展开更多
基金supported by the Volkswagen Stiftung(grant No.90233)to OG
文摘Alzheimer’s disease（AD）is the most common form of dementia representing a major problem for public health.In 2017 there were an estimated 50 million patients worldwide and this number is expected to almost double every 20years,reaching 75 million in 2030 and 131.5 million in 2050（https：//www.alz.co.uk/research/statistics）.
基金supported by the National Natural Science Foundation of China (30825014,81061120529,30970814,81371488,91132727 and 30830046)the Key Program for Clinical Medicine and Science and Technology,Jiangsu Provincial Clinical Medical Research Center,China (BL2013025)
文摘The regional specifi city of hippocampal abnormalities in late-life depression（LLD） has been demonstrated in previous studies. In this study,we sought to examine the functional connectivity（FC） patterns of hippocampal subregions in remitted late-onset depression（r LOD）,a special subtype of LLD. Fourteen r LOD patients and 18 healthy controls underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging scans at baseline and at ~21 months of follow-up. Each hippocampus was divided into three parts,the cornu ammonis（CA）,the dentate gyrus,and the subicular complex,and then six seed-based hippocampal subregional networks were established.Longitudinal changes of the six networks over time were directly compared between the rL OD and control groups. From baseline to follow-up,the r LOD group showed a greater decline in connectivity of the left CA to the bilateral posterior cingulate cortex/precuneus（PCC/PCUN）,but showed increased connectivity of the right hippocampal subregional networks with the frontal cortex（bilateral medial prefrontal cortex/anterior cingulate cortex and supplementary motor area）. Further correlative analyses revealed thatthe longitudinal changes in FC between the left CA and PCC/PCUN were positively correlated with longitudinal changes in the Symbol Digit Modalities Test（r = 0.624,P = 0.017） and the Digit Span Test（r = 0.545,P = 0.044） scores in the r LOD group. These results may provide insights into the neurobiological mechanism underlying the cognitive dysfunction in r LOD patients.
基金FC was supported by the Italian Ministry of Health(Research Grant:GR-2019–12370446)MDA was supported by the American Alzheimer’s Association(AARG-21–851219)+6 种基金the Italian Ministry of Health(Research Grant:RF-2018–12365527)Regione Lazio(PO FESR LAZIO 2014/2020,T0002E0001)the Italian Ministry of Universities and Research(Prot.2020Z73J5A)Fondazione Roma(Rome,Italy)PK was supported by an under-40 grant from the Italian Association for Alzheimer’s Research(AIRALTZH-AGYR2020)the Italian Ministry of Health(Research Grant:GR-2019–12370446)the American Alzheimer’s Association(AARG-22–922961).
文摘The last decades have witnessed huge efforts devoted to deciphering the pathological mechanisms underlying Alzheimer’s Disease(AD)and to testing new drugs,with the recent FDA approval of two anti-amyloid monoclonal antibodies for AD treatment.Beyond these drug-based experimentations,a number of pre-clinical and clinical trials are exploring the benefits of alternative treatments,such as non-invasive stimulation techniques on AD neuropathology and symptoms.Among the different non-invasive brain stimulation approaches,transcranial alternating current stimulation(tACS)is gaining particular attention due to its ability to externally control gamma oscillations.Here,we outline the current knowledge concerning the clinical efficacy,safety,ease-of-use and cost-effectiveness of tACS on early and advanced AD,applied specifically at 40 Hz frequency,and also summarise pre-clinical results on validated models of AD and ongoing patient-centred trials.
基金supported by the National Natural Science Foundation of China(81901309)the Science and Technology Funding Project to Support the High-Quality Development of China Medical University(2023JH2/20200039)+1 种基金the Basic Scientific Research Project of Institutions of Higher Learning of Liaoning Province(LJKZ0775)the Joint Plan of Science and Technology of Liaoning Province(2023-MSLH-369)the Science and Technology Innovation Team Project of China Medical University(CXTD2022007).
文摘Endosomes are crucial sites for intracellular material sorting and transportation.Endosomal transport is a critical process involved in the selective uptake,processing,and intracellular transport of substances.The equilibrium between endocytosis and circulation mediated by the endosome-centered transport pathway plays a significant role in cell homeostasis,signal transduction,and immune response.In recent years,there have been hints linking endosomal transport abnormalities to neurodegenerative diseases,including Alzheimer’s disease.Nonetheless,the related mechanisms remain unclear.Here,we provide an overview of endosomal-centered transport pathways and highlight potential physiological processes regulated by these pathways,with a particular focus on the correlation of endosomal trafficking disorders with common pathological features of neurodegenerative diseases.Additionally,we summarize potential therapeutic agents targeting endosomal trafficking for the treatment of neurodegenerative diseases.
