Aβ and Tau Prions Causing Alzheimer’s Disease

神经病理学 疾病 长寿 阿尔茨海默病 生物 转基因小鼠 痴呆 病理 转基因 医学 遗传学 基因
作者
Carlo Condello,Gregory E. Merz,Atsushi Aoyagi,William F. DeGrado,Stanley B. Prusiner
出处
期刊:Methods in molecular biology [Springer Science+Business Media]
卷期号:: 293-337 被引量:15
标识
DOI:10.1007/978-1-0716-2655-9_16
摘要

Studies show that patients with Alzheimer’s disease (AD) have both Aβ and tau prions, and thus, AD is a double-prion disease. AD patients with the greatest longevity exhibited low levels of both Aβ and tau prions; tau prions were nearly absent in the brains of almost half of the patients who lived beyond 80 years of age. Using cellular bioassays for prions in postmortem samples, we found that both Aβ and tau proteins misfold into prions leading to AD, which is either a sporadic or familial dementing disorder. Although AD is transmissible experimentally, there is no evidence that AD is either communicable or contagious. Since the progression of AD correlates poorly with insoluble Aβ in the central nervous system (CNS), it was difficult to distinguish between inert amyloids and Aβ prions. To measure the progression of AD, we devised rapid bioassays to measure the abundance of isoform-specific Aβ prions in the brains of transgenic (Tg) mice and in postmortem human CNS samples from AD victims and people who died of other neurodegenerative diseases (NDs). We found significant correlations between the longevity of individuals with AD, sex, and genetic background, despite the fact that all postmortem brain tissue had essentially the same confirmed neuropathology. Although brains from all AD patients had measurable levels of Aβ prionsPrions at death, the oldest individuals had lower Aβ prionPrions levels than the younger ones. Additionally, the long-lived individuals had low tau prionPrions levels that correlated with the extent of phosphorylated tau (p-tau). Unexpectedly, a longevity-dependent decrease in tau prionsPrions was found in spite of increasing amounts of total insoluble tau. When corrected for the abundance of insoluble tau, the tau prionPrions levels decreased exponentially with respect to the age at death with a half-time of approximately one decade, and this correlated with the abundance of phosphorylated tau. Even though our findings with tau prionsPrions were not unexpected, they were counterintuitive; thus, tau phosphorylation and tau prionPrions activity decreased exponentially with longevity in patients with AD ranging from ages 37 to 99 years. Our findings demonstrated an inverse correlation between longevity in AD patients and the abundance of neurotoxic tau prionsPrions. Moreover, our discovery may have profound implications for the selection of phenotypically distinct patient populations and the development of diagnosticsDiagnostics and effective therapeutics for AD.
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
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
研友_VZG7GZ应助岁华采纳,获得10
1秒前
小东同志发布了新的文献求助10
1秒前
gu完成签到,获得积分10
1秒前
搬运工完成签到,获得积分10
3秒前
魔幻代萱应助欣喜的迎梦采纳,获得10
4秒前
杰哥完成签到 ,获得积分10
5秒前
健康幸福平安完成签到,获得积分10
5秒前
Serena完成签到 ,获得积分10
5秒前
小远远发布了新的文献求助10
6秒前
nihau完成签到,获得积分20
6秒前
噜噜噜噜噜完成签到,获得积分10
9秒前
墨维晟完成签到 ,获得积分10
10秒前
11秒前
11秒前
limit完成签到,获得积分10
11秒前
huahua完成签到 ,获得积分10
11秒前
小马甲应助666采纳,获得10
12秒前
ccc完成签到 ,获得积分10
12秒前
13秒前
赘婿应助junjie采纳,获得10
13秒前
Chen完成签到 ,获得积分10
14秒前
细心蚂蚁发布了新的文献求助10
14秒前
guo发布了新的文献求助10
15秒前
pdx666发布了新的文献求助10
16秒前
科研通AI5应助Fjj采纳,获得10
16秒前
武汉理工材料完成签到,获得积分10
16秒前
彤彤完成签到 ,获得积分10
19秒前
泡泡茶壶o完成签到 ,获得积分10
20秒前
20秒前
yuanletong完成签到 ,获得积分10
21秒前
甜甜小蘑菇完成签到,获得积分10
23秒前
科研小民工应助ling22采纳,获得30
24秒前
岁华发布了新的文献求助10
25秒前
大饼完成签到 ,获得积分10
28秒前
迷人秋烟应助噜噜噜噜噜采纳,获得50
30秒前
zijingsy完成签到 ,获得积分10
30秒前
淡然以柳完成签到 ,获得积分10
31秒前
wqts完成签到,获得积分10
31秒前
31秒前
wqk完成签到,获得积分10
32秒前
高分求助中
Production Logging: Theoretical and Interpretive Elements 2700
Neuromuscular and Electrodiagnostic Medicine Board Review 1000
こんなに痛いのにどうして「なんでもない」と医者にいわれてしまうのでしょうか 510
The First Nuclear Era: The Life and Times of a Technological Fixer 500
Unusual formation of 4-diazo-3-nitriminopyrazoles upon acid nitration of pyrazolo[3,4-d][1,2,3]triazoles 500
岡本唐貴自伝的回想画集 500
Distinct Aggregation Behaviors and Rheological Responses of Two Terminally Functionalized Polyisoprenes with Different Quadruple Hydrogen Bonding Motifs 450
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3671598
求助须知:如何正确求助?哪些是违规求助? 3228309
关于积分的说明 9779385
捐赠科研通 2938622
什么是DOI,文献DOI怎么找? 1610143
邀请新用户注册赠送积分活动 760547
科研通“疑难数据库(出版商)”最低求助积分说明 736093