Increased Plasma Beta-Secretase 1 May Predict Conversion to Alzheimer's Disease Dementia in Individuals With Mild Cognitive Impairment.
Increased Plasma Beta-Secretase 1 May Predict Conversion to Alzheimer's Disease Dementia in Individuals With Mild Cognitive Impairment.
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DOI：
10.1016/j.biopsych.2017.02.007
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发表时间：
2018-03-01
影响因子：
10.6
通讯作者：
Hampel H
中科院分区：
文献类型：
--
作者：
Shen Y;Wang H;Sun Q;Yao H;Keegan AP;Mullan M;Wilson J;Lista S;Leyhe T;Laske C;Rujescu D;Levey A;Wallin A;Blennow K;Li R;Hampel H
在轻度认知障碍和可能的阿尔茨海默病(AD)患者的脑组织和脑脊液中，β分泌酶活性一直高于对照组。腰椎穿刺术采集脑脊液具有侵入性。我们试图确定血浆BACE1活性的存在，并确定与健康对照组(HC)相比，临床随访3年的MCI患者与诊断为可能AD痴呆的患者的潜在变化。从三个独立的国际学术记忆诊所和AD研究专家中心招募了75名可能的AD患者、96名MCI患者和53名年龄和性别匹配的HC。采用合成荧光底物酶联免疫吸附试验测定血浆BACE1活性。使用识别N-、C-和全长BACE1表位的三种不同抗体，通过Western blotting评估BACE1蛋白的表达。与HC相比，MCI患者血浆BACE1活性(Vmax)显著升高53.2%，疑似AD患者血浆BACE1活性(Vmax)显著升高68.9%。有趣的是，在随访中转化为可能的AD痴呆的MCI受试者比认知稳定的MCI受试者表现出显著更高的BACE1活性，也表现出比AD患者更高的BACE1活性水平。MCI转换者和疑似AD患者血浆BACE1活性显著升高。BACE1活性检测的敏感性为84%，特异性为88%。我们的结果表明，血浆BACE1活性可能是AD风险的一个生物标志物，并可以预测从前驱症状到可能的AD痴呆的进展。
Increased β-secretase (BACE1) activity has consistently been detected in the brain tissue and cerebrospinal fluid (CSF) of subjects with mild cognitive impairment (MCI) and probable Alzheimer’s disease (AD) compared to controls. The collection of CSF by lumbar puncture is invasive. We sought to identify the presence of plasma BACE1 activity and determine potential alterations in MCI subjects with clinical follow-ups for 3 years using patients with diagnosed probable AD dementia compared to healthy controls (HC). 75 probable AD patients, 96 MCI individuals and 53 age- and sex-matched HC were recruited from three independent international academic memory clinics and AD research expert centers. Plasma BACE1 activity was measured by a synthetic fluorescence substrate enzyme-linked immunosorbent assay. BACE1 protein expression was assessed by Western blotting using three different antibodies that recognize the epitopes of the N-, C-, and full-length BACE1. Compared to HC, plasma BACE1 activity (Vmax) significantly increased by 53.2% in MCI subjects and by 68.9% in probable AD patients. Interestingly, MCI subjects who converted to probable AD dementia at follow-ups exhibited significantly higher BACE1 activity compared to cognitively stable MCI non-converters and also showed higher levels of BACE1 activity than AD patients. The plasma BACE1 activity is significantly increased in MCI converters and probable AD patients. The sensitivities of BACE1 activity for the patients were 84% and the specificities were 88%. Our results indicate that plasma BACE1 activity may be a biomarker for AD risk and could predict progression from prodromal to probable AD dementia.
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影响因子：
168.9
作者：
Ballard, Clive;Gauthier, Serge;Jones, Emma
通讯作者：
Jones, Emma
DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
DOI：
10.1093/brain/aww160
发表时间：
2016-09
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Leuzy A;Chiotis K;Hasselbalch SG;Rinne JO;de Mendonça A;Otto M;Lleó A;Castelo-Branco M;Santana I;Johansson J;Anderl-Straub S;von Arnim CA;Beer A;Blesa R;Fortea J;Herukka SK;Portelius E;Pannee J;Zetterberg H;Blennow K;Nordberg A
通讯作者：
Nordberg A
DOI：
10.1523/jneurosci.3588-11.2011
发表时间：
2011-11-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Giusti-Rodríguez P;Gao J;Gräff J;Rei D;Soda T;Tsai LH
通讯作者：
Tsai LH