干旱区生态环境知识资源中心(Arid): Disrupted Excitation-Inhibition Balance in Cognitively Normal Individuals at Risk of Alzheimer's Disease

Arid

DOI	10.3233/JAD-230035
	Disrupted Excitation-Inhibition Balance in Cognitively Normal Individuals at Risk of Alzheimer's Disease
	Fortel, Igor; Zhan, Liang; Ajilore, Olusola; Wu, Yichao; Mackin, Scott; Leow, Alex
通讯作者	Leow, A
来源期刊	JOURNAL OF ALZHEIMERS DISEASE
ISSN	1387-2877
EISSN	1875-8908
出版年	2023
卷号	95 期号:4 页码:1449-1467
英文摘要	Background: Sex differences impact Alzheimer's disease (AD) neuropathology, but cell-to-network level dysfunctions in the prodromal phase are unclear. Alterations in hippocampal excitation-inhibition balance (EIB) have recently been linked to early AD pathology. Objective: Examine how AD risk factors (age, APOE epsilon 4, amyloid-beta) relate to hippocampal EIB in cognitively normal males and females using connectome-level measures. Methods: Individuals from the OASIS-3 cohort (age 42-95) were studied (N = 437), with a subset aged 65+ undergoing neuropsychological testing (N = 231). Results: In absence of AD risk factors (APOE epsilon 4/A beta+), whole-brain EIB decreases with age more significantly in males than females (p = 0.021, beta = -0.007). Regression modeling including APOE epsilon 4 allele carriers (A beta-) yielded a significant positive AGE-by-APOE interaction in the right hippocampus for females only (p = 0.013, beta = 0.014), persisting with inclusion of A beta+ individuals (p = 0.012, beta = 0.014). Partial correlation analyses of neuropsychological testing showed significant associations with EIB in females: positive correlations between right hippocampal EIB with categorical fluency and whole-brain EIB with the Trail Making Test (p < 0.05). Conclusions: Sex differences in EIB emerge during normal aging and progresses differently with AD risk. Results suggest APOE epsilon 4 disrupts hippocampal balance more than amyloid in females. Increased excitation correlates positively with neuropsychological performance in the female group, suggesting a duality in terms of potential beneficial effects prior to cognitive impairment. This underscores the translational relevance of APOE epsilon 4 related hyperexcitation in females, potentially informing therapeutic targets or early interventions to mitigate AD progression in this vulnerable population.
英文关键词	Alzheimer's disease amyloid-beta apolipoprotein E brain dynamics hyperexcitation excitation-inhibition balance
类型	Article
语种	英语
开放获取类型	Green Submitted
收录类别	SCI-E
WOS记录号	WOS:001086989000011
WOS关键词	BRAIN TAU DEPOSITION ; DATA SET UDS ; APOLIPOPROTEIN-E ; MODEL ; DYNAMICS ; SCALE ; NETWORKS ; GENOTYPE ; RESERVE ; AUTISM
WOS类目	Neurosciences
WOS研究方向	Neurosciences & Neurology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/397117
推荐引用方式 GB/T 7714	Fortel, Igor,Zhan, Liang,Ajilore, Olusola,et al. Disrupted Excitation-Inhibition Balance in Cognitively Normal Individuals at Risk of Alzheimer's Disease[J],2023,95(4):1449-1467.
APA	Fortel, Igor,Zhan, Liang,Ajilore, Olusola,Wu, Yichao,Mackin, Scott,&Leow, Alex.(2023).Disrupted Excitation-Inhibition Balance in Cognitively Normal Individuals at Risk of Alzheimer's Disease.JOURNAL OF ALZHEIMERS DISEASE,95(4),1449-1467.
MLA	Fortel, Igor,et al."Disrupted Excitation-Inhibition Balance in Cognitively Normal Individuals at Risk of Alzheimer's Disease".JOURNAL OF ALZHEIMERS DISEASE 95.4(2023):1449-1467.