机构：[1]Innovation Center for Neurological Disorders and Department of Neurology,Xuanwu Hospital, Capital Medical University, National Clinical ResearchCenter for Geriatric Diseases, Beijing, People’s Republic of China首都医科大学宣武医院神经疾病高创中心（北京学者工作室）神经内科国家老年疾病临床医学研究中心[2]Beijing KeyLaboratory of Geriatric Cognitive Disorders, Beijing, People’s Republic ofChina[3]Clinical Center for Neurodegenerative Disease and MemoryImpairment, Capital Medical University, Beijing, People’s Republic of China[4]Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing,People’s Republic of China[5]Guang’anmen Hospital, China Academy ofChinese Medical Sciences, Beijing, China
Although structural and functional changes of the striatum and hippocampus are present in familial Alzheimer's disease, little is known about the effects of specific gene mutation or disease progression on their related neural circuits. This study was to evaluate the effects of known pathogenic gene mutation and disease progression on the striatum- and hippocampus-related neural circuits, including frontostriatal and hippocampus-posterior cingulate cortex (PCC) pathways.
A total of 102 healthy mutation non-carriers, 40 presymptomatic mutation carriers (PMC), and 30 symptomatic mutation carriers (SMC) of amyloid precursor protein (APP), presenilin 1 (PS1), or presenilin 2 gene, with T1 structural MRI, diffusion tensor imaging, and resting-state functional MRI were included. Representative neural circuits and their key nodes were obtained, including bilateral caudate-rostral middle frontal gyrus (rMFG), putamen-rMFG, and hippocampus-PCC. Volumes, diffusion indices, and functional connectivity of circuits were compared between groups and correlated with neuropsychological and clinical measures.
In PMC, APP gene mutation carriers showed impaired diffusion indices of caudate-rMFG and putamen-rMFG circuits; PS1 gene mutation carriers showed increased fiber numbers of putamen-rMFG circuit. SMC showed increased diffusivity of the left hippocampus-PCC circuit and volume reduction of all regions as compared with PMC. Imaging measures especially axial diffusivity of the representative circuits were correlated with neuropsychological measures.
APP and PS1 gene mutations affect frontostriatal circuits in a different manner in familial Alzheimer's disease; disease progression primarily affects the structure of hippocampus-PCC circuit. The structural connectivity of both frontostriatal and hippocampus-PCC circuits is associated with general cognitive function. Such findings may provide further information about the imaging biomarkers for early identification and prognosis of familial Alzheimer's disease, and pave the way for early diagnosis, gene- or circuit-targeted treatment, and even prevention.
基金：
the research grants to MQ from Beijing
Postdoctoral Research Foundation and research grants to JJ from the
National Natural Science Foundation of China for the Key Project (81530036),
the National Key Scientific Instrument and Equipment Development Project
(31627803), Beijing Municipal Administration of Hospitals for Mission
Program (SML20150801), Beijing Municipal Human Resources and Social
Security Bureau for the Beijing Scholars Program, Beijing Municipal Science &
Technology Commission for the Beijing Brain Initiative (Z161100000216137),
and Beijing Municipal Commission of Health and Family Planning
(PXM2018_026283_000002).
第一作者机构：[1]Innovation Center for Neurological Disorders and Department of Neurology,Xuanwu Hospital, Capital Medical University, National Clinical ResearchCenter for Geriatric Diseases, Beijing, People’s Republic of China[2]Beijing KeyLaboratory of Geriatric Cognitive Disorders, Beijing, People’s Republic ofChina[3]Clinical Center for Neurodegenerative Disease and MemoryImpairment, Capital Medical University, Beijing, People’s Republic of China[4]Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing,People’s Republic of China
通讯作者：
通讯机构：[1]Innovation Center for Neurological Disorders and Department of Neurology,Xuanwu Hospital, Capital Medical University, National Clinical ResearchCenter for Geriatric Diseases, Beijing, People’s Republic of China[2]Beijing KeyLaboratory of Geriatric Cognitive Disorders, Beijing, People’s Republic ofChina[3]Clinical Center for Neurodegenerative Disease and MemoryImpairment, Capital Medical University, Beijing, People’s Republic of China[4]Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing,People’s Republic of China
推荐引用方式(GB/T 7714)：
Meina Quan,Tan Zhao,Yi Tang,et al.Effects of gene mutation and disease progression on representative neural circuits in familial Alzheimer's disease.[J].ALZHEIMERS RESEARCH & THERAPY.2020,12(1):14.doi:10.1186/s13195-019-0572-2.
APA：
Meina Quan,Tan Zhao,Yi Tang,Ping Luo,Wei Wang...&Jianping Jia.(2020).Effects of gene mutation and disease progression on representative neural circuits in familial Alzheimer's disease..ALZHEIMERS RESEARCH & THERAPY,12,(1)
MLA：
Meina Quan,et al."Effects of gene mutation and disease progression on representative neural circuits in familial Alzheimer's disease.".ALZHEIMERS RESEARCH & THERAPY 12..1(2020):14
医学