PICALM rs3851179 Variants Modulate Left Postcentral Cortex Thickness, CSF Amyloid β42, and Phosphorylated Tau in the Elderly.
PICALM rs3851179 Variants Modulate Left Postcentral Cortex Thickness, CSF Amyloid β42, and Phosphorylated Tau in the Elderly.
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DOI：
10.3390/brainsci12121681
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发表时间：
2022-12-07
期刊：
影响因子：
3.3
通讯作者：
Dai, Hui
中科院分区：
文献类型：
--
作者：
Wu, Zhiwei;Yang, Yiwen;Song, Ziyang;Ma, Mengya;Feng, Mengmeng;Liu, Yuanqing;Xing, Hanqi;Chang, Yue;Dai, Hui
PICALM rs3851179是与迟发性阿尔茨海默病（LOAD）易感性最相关的基因之一，在调节淀粉样前体蛋白和淀粉样β（Aβ）转胞吞中起关键作用。为探讨PICALM和AD连续分期对皮质厚度、CSF Aβ和tau蛋白的影响，招募了188名认知正常对照、261名MCI患者和140名早期LOAD患者，每组分为rs3851179 A携带者和GG携带者。采用全因子协方差分析方法分析AD持续期和PICALM的主效应和交互效应。AD持续期和PICALM对皮质厚度和CSF生物标志物的交互作用不显著。PICALM的主要效应是左侧中央后皮质厚度，A基因携带者的皮质厚度小于GG基因携带者。与GG携带者相比，rs3851179 A携带者显示出较高的Aβ42水平和Aβ42/40比值，以及较低的P/T-tau比值。在LOAD患者中，A携带者的MMSE评分较高。结论：PICALM的主要效应与AD持续期无关，PICLAM rs3851179基因型可调节左后中央皮质厚度、Aβ42水平和P/T-tau比值。rs3851179 A等位基因可能保护LOAD患者的认知功能。
PICALM rs3851179, one of the genes most frequently linked to susceptibility of late-onset Alzheimer’s disease (LOAD), plays a crucial role in regulating amyloid precursor protein, and amyloid β (Aβ) transcytosis. To explore the effects of PICALM and AD continuum stage on cortex thickness, CSF Aβ, and tau, 188 cognitively normal controls, 261 MCI patients, and 140 early LOAD patients were recruited, and each group was divided into rs3851179 A-carriers and GG-carriers. A full factorial ANCOVA was used to analyze the main effects and interactive effects of AD continuum stage, and PICALM. The interactive effects of AD continuum stage and PICALM on cortex thickness and CSF biomarkers were not significant. The main effect of PICALM was significant on the left postcentral cortex thickness, and the cortex thickness of A-carriers was less than that of GG-carriers. The rs3851179 A-carriers displayed higher Aβ42 levels and Aβ42/40 ratios, and lower P/T–tau ratios, compared with GG-carriers. A higher MMSE score was found in A-carriers among the LOAD patients. In conclusion, the main effects of PICALM were independent of AD continuum stage, and PICLAM rs3851179 genotypes may modulate left postcentral cortex thickness, Aβ42 level, and P/T–tau ratio. The rs3851179 A-allele may protect the cognitive function of LOAD patients.
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影响因子：
9.9
作者：
Grothe MJ;Barthel H;Sepulcre J;Dyrba M;Sabri O;Teipel SJ;Alzheimer's Disease Neuroimaging Initiative
通讯作者：
Alzheimer's Disease Neuroimaging Initiative
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：
25
作者：
Damasio, AR;Grabowski, TJ;Hichwa, RD
通讯作者：
Hichwa, RD
影响因子：
25
作者：
Glasser MF;Smith SM;Marcus DS;Andersson JL;Auerbach EJ;Behrens TE;Coalson TS;Harms MP;Jenkinson M;Moeller S;Robinson EC;Sotiropoulos SN;Xu J;Yacoub E;Ugurbil K;Van Essen DC
通讯作者：
Van Essen DC
影响因子：
4
作者：
Ashford, J. Wesson;Mortimer, James A.
通讯作者：
Mortimer, James A.