Systemic perturbations of the kynurenine pathway precede progression to dementia independently of amyloid-β

痴呆 犬尿氨酸 代谢物 犬尿氨酸途径 喹啉酸 混淆 神经保护 疾病 内科学 淀粉样蛋白(真菌学) 新喋呤 脑脊液 医学 优势比 心理学 神经科学 肿瘤科 病理 生物 生物化学 色氨酸 氨基酸
作者
Marcela I. Cespedes,Kelly R. Jacobs,Paul Maruff,Alan Rembach,Christopher Fowler,Brett Trounson,Kelly K. Pertile,Rebecca Rumble,Stephanie R. Rainey‐Smith,Christopher C. Rowe,Victor L. Villemagne,Pierrick Bourgeat,Chai K. Lim,Pratishtha Chatterjee,Ralph N. Martins,Arne Ittner,Colin L. Masters,James D. Doecke,Gilles J. Guillemin,David B. Lovejoy
出处
期刊:Neurobiology of Disease [Elsevier]
卷期号:171: 105783-105783 被引量:8
标识
DOI:10.1016/j.nbd.2022.105783
摘要

Increasing evidence suggests that kynurenine pathway (KP) dyshomeostasis may promote disease progression in dementia. Studies in Alzheimer's disease (AD) patients confirm KP dyshomeostasis in plasma and cerebrospinal fluid (CSF) which correlates with amyloid-β and tau pathology. Herein, we performed the first comprehensive study assessing baseline levels of KP metabolites in participants enrolling in the Australian Imaging Biomarkers Flagship Study of Aging. Our purpose was to test the hypothesis that changes in KP metabolites may be biomarkers of dementia processes that are largely silent. We used a cross-sectional analytical approach to assess non-progressors (N = 73); cognitively normal (CN) or mild cognitive impairment (MCI) participants at baseline and throughout the study, and progressors (N = 166); CN or MCI at baseline but progressing to either MCI or AD during the study. Significant KP changes in progressors included increased 3-hydroxyanthranilic acid (3-HAA) and 3-hydroxyanthranilic acid/anthranilic acid (3-HAA/AA) ratio, the latter having the largest effect on the odds of an individual being a progressor (OR 35.3; 95% CI between 14 and 104). 3-HAA levels were hence surprisingly bi-phasic, high in progressors but low in non-progressors or participants who had already transitioned to MCI or dementia. This is a new, unexpected and interesting result, as most studies of the KP in neurodegenerative disease show reduced 3-HAA/AA ratio after diagnosis. The neuroprotective metabolite picolinic acid was also significantly decreased while the neurotoxic metabolite 3-hydroxykynurenine increased in progressors. These results were significant even after adjustment for confounders. Considering the magnitude of the OR to predict change in cognition, it is important that these findings are replicated in other populations. Independent validation of our findings may confirm the utility of 3-HAA/AA ratio to predict change in cognition leading to dementia in clinical settings.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
Cassie应助科研通管家采纳,获得10
刚刚
gogozoco发布了新的文献求助10
刚刚
刘澄伊应助科研通管家采纳,获得10
刚刚
ding应助科研通管家采纳,获得10
刚刚
susu应助科研通管家采纳,获得10
刚刚
烟花应助科研通管家采纳,获得10
刚刚
幸福大白发布了新的文献求助10
刚刚
刚刚
1秒前
Jayce发布了新的文献求助30
1秒前
喷泡的兔子完成签到,获得积分10
2秒前
chi123完成签到 ,获得积分10
2秒前
大小罐子完成签到,获得积分10
3秒前
3秒前
呐喊也抒情完成签到,获得积分10
4秒前
5秒前
调皮剑鬼发布了新的文献求助10
5秒前
田様应助秋以南采纳,获得10
5秒前
共享精神应助licheng采纳,获得10
5秒前
VDC发布了新的文献求助30
5秒前
5秒前
乐观蚂蚁完成签到 ,获得积分10
6秒前
Original完成签到,获得积分10
7秒前
王青青发布了新的文献求助10
7秒前
7秒前
7秒前
8秒前
xg完成签到,获得积分10
8秒前
幸福大白发布了新的文献求助10
9秒前
科研通AI2S应助肥仔采纳,获得10
9秒前
嗷嗷嗷完成签到,获得积分10
9秒前
9秒前
十文字完成签到,获得积分20
9秒前
lllyyysss发布了新的文献求助10
10秒前
完美傲柔发布了新的文献求助10
10秒前
10秒前
小深完成签到,获得积分10
10秒前
科研通AI2S应助风中夜天采纳,获得10
11秒前
科研通AI2S应助kokokosini123采纳,获得10
11秒前
蛋挞蛋挞发布了新的文献求助10
11秒前
高分求助中
Evolution 10000
Becoming: An Introduction to Jung's Concept of Individuation 600
Distribution Dependent Stochastic Differential Equations 500
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
A new species of Velataspis (Hemiptera Coccoidea Diaspididae) from tea in Assam 500
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 500
The Kinetic Nitration and Basicity of 1,2,4-Triazol-5-ones 440
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3159180
求助须知:如何正确求助?哪些是违规求助? 2810321
关于积分的说明 7887314
捐赠科研通 2469183
什么是DOI,文献DOI怎么找? 1314687
科研通“疑难数据库(出版商)”最低求助积分说明 630682
版权声明 602012