Since the establishment of the biomarker-based A-T-N(Amyloid/Tau/Neurodegeneration)framework in Alzheimer's disease(AD),the diagnosis of AD has become more precise,and cerebrospinal fluid tests and positron emissi...Since the establishment of the biomarker-based A-T-N(Amyloid/Tau/Neurodegeneration)framework in Alzheimer's disease(AD),the diagnosis of AD has become more precise,and cerebrospinal fluid tests and positron emission tomography examinations based on this framework have become widely accepted.However,the A-T-N framework does not encompass the whole spectrum of AD pathologies,and problems with invasiveness and high cost limit the application of the above diagnostic methods aimed at the central nervous system.Therefore,we suggest the addition of an“X”to the A-T-N framework and a focus on peripheral biomarkers in the diagnosis of AD.In this review,we retrospectively describe the recent progress in biomarkers based on the A-T-N-X framework,analyze the problems,and present our perspectives on the diagnosis of AD.展开更多
The extracellular domain(p75ECD)of p75 neurotrophin receptor(p75NTR)antagonizes Aβ neurotoxicity and promotes Aβclearance in Alzheimer’s disease(AD).The impaired shedding of p75ECD is a key pathological process in ...The extracellular domain(p75ECD)of p75 neurotrophin receptor(p75NTR)antagonizes Aβ neurotoxicity and promotes Aβclearance in Alzheimer’s disease(AD).The impaired shedding of p75ECD is a key pathological process in AD,but its regulatory mechanism is largely unknown.This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD(p75ECD-NAbs)in AD patients and their effects on AD pathology.We found that the cerebrospinal fluid(CSF)level of p75ECD-NAbs was increased in AD,and negatively associated with the CSF levels of p75ECD.Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain,as well as worse cognitive functions than the control groups,which were immunized with Re-p75ECD(the reverse sequence of p75ECD)and phosphate-buffered saline,respectively.These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance,providing a novel insight into the role of autoimmunity and p75NTR in AD.展开更多
Advances in Alzheimer's disease(AD)research have deepened our understanding,yet the mechanisms driving its progression remain unclear.Although a range of in vivo biomarkers is now available(e.g.,measurements of am...Advances in Alzheimer's disease(AD)research have deepened our understanding,yet the mechanisms driving its progression remain unclear.Although a range of in vivo biomarkers is now available(e.g.,measurements of amyloidbeta(Aβ)and ta u accumulation-the molecular hallmarks of AD-structural magnetic resonance imaging(MRI),assessments of brain metabolism,and,more recently,blood-based markers),a definitive diagnosis of AD continues to be challenging.For example,Frisoni et al.展开更多
基金supported by the National Natural Science Foundation of China(81930028)the National Key R&D Program of China(2018YFA0109600).
文摘Since the establishment of the biomarker-based A-T-N(Amyloid/Tau/Neurodegeneration)framework in Alzheimer's disease(AD),the diagnosis of AD has become more precise,and cerebrospinal fluid tests and positron emission tomography examinations based on this framework have become widely accepted.However,the A-T-N framework does not encompass the whole spectrum of AD pathologies,and problems with invasiveness and high cost limit the application of the above diagnostic methods aimed at the central nervous system.Therefore,we suggest the addition of an“X”to the A-T-N framework and a focus on peripheral biomarkers in the diagnosis of AD.In this review,we retrospectively describe the recent progress in biomarkers based on the A-T-N-X framework,analyze the problems,and present our perspectives on the diagnosis of AD.
基金supported by the National Natural Science Foundation of China(81870860).
文摘The extracellular domain(p75ECD)of p75 neurotrophin receptor(p75NTR)antagonizes Aβ neurotoxicity and promotes Aβclearance in Alzheimer’s disease(AD).The impaired shedding of p75ECD is a key pathological process in AD,but its regulatory mechanism is largely unknown.This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD(p75ECD-NAbs)in AD patients and their effects on AD pathology.We found that the cerebrospinal fluid(CSF)level of p75ECD-NAbs was increased in AD,and negatively associated with the CSF levels of p75ECD.Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain,as well as worse cognitive functions than the control groups,which were immunized with Re-p75ECD(the reverse sequence of p75ECD)and phosphate-buffered saline,respectively.These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance,providing a novel insight into the role of autoimmunity and p75NTR in AD.
文摘Advances in Alzheimer's disease(AD)research have deepened our understanding,yet the mechanisms driving its progression remain unclear.Although a range of in vivo biomarkers is now available(e.g.,measurements of amyloidbeta(Aβ)and ta u accumulation-the molecular hallmarks of AD-structural magnetic resonance imaging(MRI),assessments of brain metabolism,and,more recently,blood-based markers),a definitive diagnosis of AD continues to be challenging.For example,Frisoni et al.
