Impact of APOE-ε4 carriage on the onset and rates of neocortical Aβ-amyloid deposition.
Impact of APOE-ε4 carriage on the onset and rates of neocortical Aβ-amyloid deposition.
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APOE-ε4载体对新皮质Aβ-淀粉样蛋白沉积的发作和速率的影响。
DOI：
10.1016/j.neurobiolaging.2020.06.001
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发表时间：
2020-11
影响因子：
4.2
通讯作者：
AIBL Research Group
中科院分区：
文献类型：
--
作者：
Burnham SC;Laws SM;Budgeon CA;Doré V;Porter T;Bourgeat P;Buckley RF;Murray K;Ellis KA;Turlach BA;Salvado O;Ames D;Martins RN;Rentz D;Masters CL;Rowe CC;Villemagne VL;Alzheimer's Disease Neuroimaging Initiative;AIBL Research Group
新皮质Aβ-淀粉样蛋白沉积是阿尔茨海默病（AD）的标志性病理特征之一，在临床症状出现前几十年就开始了。随着临床试验转向二级甚至一级预防，了解新皮质Aβ-淀粉样蛋白沉积的速率和Aβ-淀粉样蛋白沉积变得异常的年龄对于优化这些试验的时机至关重要。由于APOE-ε4携带被认为调节临床发病年龄，因此了解APOE-ε4携带对新皮质Aβ-淀粉样蛋白沉积变得异常的年龄的影响也很重要。在这里，我们发现，对于455名随访超过3年的参与者，平均在72岁时达到新皮质Aβ-淀粉样蛋白的异常水平（66.5-77.1）。APOE-ε4携带者在63岁（59.6-70.3）时达到异常水平较早，而非携带者在78岁（76.1-84.4）时达到阈值较晚。在Aβ-淀粉样蛋白水平达到异常后，APOE-ε4携带者和非携带者之间的沉积率没有差异。这些结果表明，希望在疾病的最早阶段招募的一级和二级预防试验应针对60至66岁的APOE-ε4携带者和76至84岁的非携带者。
Neocortical Aβ-amyloid deposition, one of the hallmark pathologic features of Alzheimer’s disease (AD), begins decades prior to the presence of clinical symptoms. As clinical trials move to secondary and even primary prevention, understanding the rates of neocortical Aβ-amyloid deposition and the age at which Aβ-amyloid deposition becomes abnormal is crucial for optimising the timing of these trials. As APOE-ε4 carriage is thought to modulate the age of clinical onset, it is also important to understand the impact of APOE-ε4 carriage on the age at which neocortical Aβ-amyloid deposition becomes abnormal. Here, we show that, for 455 participants with over three years of follow-up, abnormal levels of neocortical Aβ-amyloid were reached on average at age 72 (66.5-77.1). The APOE-ε4 carriers reached abnormal levels earlier at age 63 (59.6-70.3), however, non-carriers reached the threshold later at age 78 (76.1-84.4). No differences in rates of deposition were observed between APOE-ε4 carriers and non-carriers after abnormal Aβ-amyloid levels had been reached. These results suggest that primary and secondary prevention trials, looking to recruit at the earliest stages of disease, should target APOE-ε4 carriers between the ages of 60 and 66 and non-carriers between the ages of 76 and 84.
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影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
影响因子：
9.9
作者：
CORDER, EH;SAUNDERS, AM;HAINES, JL
通讯作者：
HAINES, JL
影响因子：
120.7
作者：
Jansen, Willemijn J.;Ossenkoppele, Rik;Knol, Dirk L.;Tijms, Betty M.;Scheltens, Philip;Verhey, Frans R. J.;Visser, Pieter Jelle
通讯作者：
Visser, Pieter Jelle
DOI：
10.1073/pnas.0900345106
发表时间：
2009-04-21
影响因子：
11.1
作者：
Reiman, Eric M.;Chen, Kewei;Caselli, Richard J.
通讯作者：
Caselli, Richard J.
DOI：
10.1016/j.dadm.2019.01.005
发表时间：
2019-12-01
影响因子：
5.3
作者：
Bilgel, Murat;Jedynak, Bruno M.
通讯作者：
Jedynak, Bruno M.