Alzheimer’s disease(AD)is a primary cause of dementia.AD is a neurodegenerative disorder,characterized by synapses loss,extracellular amyloid plaques composed of the amyloid-βpeptide(Aβ)and intracellular aggregates...Alzheimer’s disease(AD)is a primary cause of dementia.AD is a neurodegenerative disorder,characterized by synapses loss,extracellular amyloid plaques composed of the amyloid-βpeptide(Aβ)and intracellular aggregates of hyperphosphorylated tau protein.AD is a complex disease linked to multiple interacting factors,both environmental and genetic,which can contribute to the onset and severity of the disease.Longitudinal studies have highlighted several cardiovascular risk factors that can increase the risk of AD.The genetic landscape of AD has changed dramatically in recent decades.Early studies identified mutations in the amyloid precursor protein gene(APP)as well as proteins that are involved in the enzymatic cleavage of APP to toxicβ-amyloid(Aβ),namely presenilin-1 and presnilin-2.However,these mutations were found in familial cases of early-onset AD,while the causes of sporadic late-onset AD are still unknown.The latest advances in Genomewide Association Studies(GWAS),sequencing,and bioinformatics have begun to unravel the complex genetic architecture of the sporadic form of AD.GWAS were able to uncover common variants with high frequency in the population that individually carried low risk(Robinson et al.,2017).The advent of next-generation and thirdgeneration sequencing platforms shows great promise in further unravelling the genetics of AD.展开更多
Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because ...Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because of the large number of voxels in the brain,multiple comparison correction(MCC)must be performed to reduce false positive rates,and a smaller P value(usually including either liberal or stringent MCC)is widely recommended[1].展开更多
文摘Alzheimer’s disease(AD)is a primary cause of dementia.AD is a neurodegenerative disorder,characterized by synapses loss,extracellular amyloid plaques composed of the amyloid-βpeptide(Aβ)and intracellular aggregates of hyperphosphorylated tau protein.AD is a complex disease linked to multiple interacting factors,both environmental and genetic,which can contribute to the onset and severity of the disease.Longitudinal studies have highlighted several cardiovascular risk factors that can increase the risk of AD.The genetic landscape of AD has changed dramatically in recent decades.Early studies identified mutations in the amyloid precursor protein gene(APP)as well as proteins that are involved in the enzymatic cleavage of APP to toxicβ-amyloid(Aβ),namely presenilin-1 and presnilin-2.However,these mutations were found in familial cases of early-onset AD,while the causes of sporadic late-onset AD are still unknown.The latest advances in Genomewide Association Studies(GWAS),sequencing,and bioinformatics have begun to unravel the complex genetic architecture of the sporadic form of AD.GWAS were able to uncover common variants with high frequency in the population that individually carried low risk(Robinson et al.,2017).The advent of next-generation and thirdgeneration sequencing platforms shows great promise in further unravelling the genetics of AD.
基金the National Natural Science Foundation of China(81520108016,81661148045,and 31471084 to Yu-Feng Zang81671774 and 81630031 to Chao-Gan Yan+11 种基金81571228 to Tao Wu61571047 to Xia Wu81701664 to Jian Wang,81471654 to Biao Huang81701671 to Wei-Guo Liu82001898 to Xi-Ze Jia81771820,81371519 and 81571654 to Wei Luo)Henry G Leong Endowed Professorship in Neurology to Shu-Leong Ho and Shirley YY Pang,BRC for Mental Health at South London and Maudsley NHS Foundation Trust and by the Sackler Institute to Grainne McAlonan,NIH(2R01AG006457 to Fay B.Horak1RC4NS073008-01 and P50NS062684 to Tara Madhyastha)NINDS Intramural Research Program to Mark HallettStart-up Funds for Leading Talents at Beijing Normal UniversityNational Basic Science Data Center‘‘Chinese Data-sharing Warehouse for In-vivo Imaging Brain”(NBSDC-DB-15)to Xi-Nian ZuoGrant NU20-04-00294 of the Agency for Health Research,Czech Republic to Lenka Krajcovicova and Irena Rektorova。
文摘Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because of the large number of voxels in the brain,multiple comparison correction(MCC)must be performed to reduce false positive rates,and a smaller P value(usually including either liberal or stringent MCC)is widely recommended[1].
