Association of accelerated long-term forgetting and senescence-related blood-borne factors in asymptomatic individuals from families with autosomal dominant Alzheimer's disease.
机构：[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St, 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.
Accelerated long-term forgetting has been identified in preclinical Alzheimer's disease (AD) and is attributed to a selective impairment of memory consolidation in which the hippocampus plays a key role. As blood may contain multiple senescence-related factors that involved in neurogenesis and synaptic plasticity in the hippocampus, we tested whether there is an association between blood-borne factors and accelerated long-term forgetting in asymptomatic individuals from families with autosomal dominant AD (ADAD).
We analyzed data of 39 asymptomatic participants (n = 18 ADAD mutation carriers, n = 21 non-carriers) from the Chinese Familial Alzheimer's Disease Network (CFAN) study. Long-term forgetting rates were calculated based on recall or recognition of two materials (word list and complex figure) at three delays comprising immediate, 30 min, and 7 days. Peripheral blood concentrations of candidate pro-aging factors (CC chemokine ligand 11 [CCL11] and monocyte chemotactic protein 1 [MCP1]) and rejuvenation factors (growth differentiation factor 11 [GDF11], thrombospondin-4 [THBS4], and secreted protein acidic and rich in cysteine like 1 [SPARCL1]) were evaluated in all participants.
Despite normal performance on standard 30-min delayed testing, mutation carriers exhibited accelerated forgetting of verbal and visual material over 7 days in comparison with matched non-carriers. In the whole sample, lower plasma THBS4 was associated with accelerated long-term forgetting in list recall (β = -0.46, p = 0.002), figure recall (β = -0.44, p = 0.004), and list recognition (β = -0.37, p = 0.010). Additionally, higher plasma GDF11 and CCL11 were both associated with accelerated long-term forgetting (GDF11 versus figure recall: β = 0.39, p = 0.007; CCL11 versus list recognition: β = 0.44, p = 0.002).
Accelerated long-term forgetting is a cognitive feature of presymptomatic AD. Senescence-related blood-borne factors, especially THBS4, GDF11, and CCL11, may be promising biomarkers for the prediction of accelerated long-term forgetting.
基金：
This study was supported by the Key Project of the National Natural Science
Foundation of China (81530036), the National Key Scientific Instrument and
Equipment Development Project (31627803), the Key Project of the National
Natural Science Foundation of China (U20A20354), Beijing Scholars Program,
and Beijing Brain Initiative from Beijing Municipal Science & Technology
Commission (Z201100005520016, Z201100005520017).
第一作者机构：[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun St, Beijing, China.
通讯作者：
推荐引用方式(GB/T 7714)：
Jianwei Yang,Chaojun Kong,Longfei Jia,et al.Association of accelerated long-term forgetting and senescence-related blood-borne factors in asymptomatic individuals from families with autosomal dominant Alzheimer's disease.[J].ALZHEIMERS RESEARCH & THERAPY.2021,13(1):doi:10.1186/s13195-021-00845-0.
APA：
Jianwei Yang,Chaojun Kong,Longfei Jia,Tingting Li,Meina Quan...&Jianping Jia.(2021).Association of accelerated long-term forgetting and senescence-related blood-borne factors in asymptomatic individuals from families with autosomal dominant Alzheimer's disease..ALZHEIMERS RESEARCH & THERAPY,13,(1)
MLA：
Jianwei Yang,et al."Association of accelerated long-term forgetting and senescence-related blood-borne factors in asymptomatic individuals from families with autosomal dominant Alzheimer's disease.".ALZHEIMERS RESEARCH & THERAPY 13..1(2021)
医学