机构：[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.神经科系统神经内科首都医科大学宣武医院[2]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China.[3]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China.[4]Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.[5]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China.
Synaptic degeneration has been suggested as an early pathological event that strongly correlates with severity of dementia in Alzheimer's disease (AD). However, changes in longitudinal cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) as a synaptic biomarker in the AD continuum remain unclear.To assess the trajectory of CSF GAP-43 with AD progression and its association with other AD hallmarks.CSF GAP-43 was analyzed in 788 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including 246 cognitively normal (CN) individuals, 415 individuals with mild cognitive impairment (MCI), and 127 with AD dementia based on cognitive assessments. The associations between a multimodal classification scheme with amyloid-β (Aβ), tau, and neurodegeneration, and changes in CSF GAP-43 over time were also analyzed.CSF GAP-43 levels were increased at baseline in MCI and dementia patients, and increased significantly over time in the preclinical (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stages of AD. Higher levels of CSF GAP-43 were also associated with higher CSF phosphorylated tau (p-tau) and total tau (t-tau), cerebral amyloid deposition and hypometabolism on positron emission tomography, the hippocampus and middle temporal atrophy, and cognitive performance deterioration at baseline and follow-up. Furthermore, CSF GAP-43 may assist in effectively predicting the probability of dementia onset at 2- or 4-year follow-up.CSF GAP-43 can be used as a potential biomarker associated with synaptic degeneration in subjects with AD; it may also be useful for tracking the disease progression and for monitoring the effects of clinical trials.
基金：
This study was supported the Key Project of 575
the National Natural Science Foundation of China 576
(81530036); the National Key Scientific Instrument 577
and Equipment Development Project (31627803); 578
the Key Project of the National Natural Sci- 579
ence Foundation of China (U20A20354); Beijing 580
Scholars Program; Beijing Brain Initiative from Bei- 581
jing Municipal Science & Technology Commission 582
(Z201100005520016, Z201100005520017)
第一作者机构：[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
共同第一作者：
通讯作者：
通讯机构：[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.[2]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China.[3]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China.[4]Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.[5]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, China.[*1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, 100053, Beijing, China
推荐引用方式(GB/T 7714)：
Zhang Heng,Lyu Diyang,Jia Jianping.The Trajectory of Cerebrospinal Fluid Growth-Associated Protein 43 in the Alzheimer's Disease Continuum: A Longitudinal Study.[J].JOURNAL OF ALZHEIMERS DISEASE.2022,85(4):1441-1452.doi:10.3233/JAD-215456.
APA：
Zhang Heng,Lyu Diyang&Jia Jianping.(2022).The Trajectory of Cerebrospinal Fluid Growth-Associated Protein 43 in the Alzheimer's Disease Continuum: A Longitudinal Study..JOURNAL OF ALZHEIMERS DISEASE,85,(4)
MLA：
Zhang Heng,et al."The Trajectory of Cerebrospinal Fluid Growth-Associated Protein 43 in the Alzheimer's Disease Continuum: A Longitudinal Study.".JOURNAL OF ALZHEIMERS DISEASE 85..4(2022):1441-1452
