Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project


Por: Moreno-Grau, S, de Rojas, I, Hernandez, I, Quintela, I, Montrreal, L, Alegret, M, Hernandez-Olasagarre, B, Madrid, L, Gonzalez-Perez, A, Maronas, O, Rosende-Roca, M, Mauleon, A, Vargas, L, Lafuente, A, Abdelnour, C, Rodriguez-Gomez, O, Gil, S, Santos-Santos, MA, Espinosa, A, Ortega, G, Sanabria, A, Perez-Cordon, A, Canabate, P, Moreno, M, Preckler, S, Ruiz, S, Aguilera, N, Pineda, JA, Macias, J, Alarcon-Martin, E, Sotolongo-Grau, O, Marquie, M, Monte-Rubio, G, Valero, S, Benaque, A, Clarimon, J, Bullido, MJ, Garcia-Ribas, G, Pastor, P, Sanchez-Juan, P, Alvarez, V, Pinol-Ripoll, G, Garcia-Alberca, JM, Royo, JL, Franco, E, Mir, P, Calero, M, Medina, M, Rabano, A, Avila, J, Antunez, C, Real, LM, Orellana, A, Carracedo, A, Saez, ME, Tarraga, L, Boada, M, Ruiz, A, Alarcon, E, Buendia, M, Corbaton, A, Diego, S, Gailhajenet, A, Gonzalez, PG, Guitart, M, Ibarria, M, Martin, E, Martinez, MT, Pancho, A, Peleja, E, Pineda, JA, Real, LM, Serrano-Rios, M, Adarmes-Gomez, AD, Alvarez, I, Amer-Ferrer, G, Antequera, M, Baquero, M, Bernal, M, Blesa, R, Buiza-Rueda, D, Bullido, MJ, Burguera, JA, Carrillo, F, Carrion-Claro, M, Casajeros, MJ, Cruz-Gamero, JM, de Pancorbo, MM, del Ser, T, Diez-Fairen, M, Fortea, J, Frank-Garcia, A, Madrona, SG, Gomez-Garre, P, Hevilla, S, Jesus, S, Espinosa, MAL, Lage, C, Legaz, A, Lleo, A, de Munain, AL, Lopez-Garcia, S, Macias, D, Manzanares, S, Marin, M, Marin-Munoz, J, Marin, T, Montes, AM, Martinez, B, Martinez, C, Martinez, V, Alvarez, PML, Iriarte, MM, Menendez-Gonzalez, M, Molinuevo, JL, Pastor, AB, Tur, JP, Perinan-Tocino, T, de Asua, DR, Rodrigo, S, Rodriguez-Rodriguez, E, Diaz, RSD, Sastre, E, Vicente, MP, Vivancos, L

Publicada: 1 oct 2019
Resumen:
Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.

Filiaciones:
Moreno-Grau, S:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Natl Inst Hlth Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

de Rojas, I:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Hernandez, I:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Natl Inst Hlth Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

Quintela, I:
 Univ Santiago de Compostela, Grp Med Xenom, Ctr Nacl Genotipado CEGEN, PRB3,ISCIII, Santiago De Compostela, Spain

 Univ Malaga, Sch Med, Dept Surg Biochem & Mol Biol, Malaga, Spain

Montrreal, L:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Alegret, M:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Natl Inst Hlth Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

Hernandez-Olasagarre, B:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Madrid, L:
 Ctr Andaluz Estudios Bioinformat, CAEBI, Seville, Spain

Gonzalez-Perez, A:
 Ctr Andaluz Estudios Bioinformat, CAEBI, Seville, Spain

Maronas, O:
 Univ Santiago de Compostela, Grp Med Xenom, Ctr Nacl Genotipado CEGEN, PRB3,ISCIII, Santiago De Compostela, Spain

Rosende-Roca, M:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Mauleon, A:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Vargas, L:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Lafuente, A:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Abdelnour, C:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Natl Inst Hlth Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

Rodriguez-Gomez, O:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Natl Inst Hlth Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

Gil, S:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Santos-Santos, MA:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Espinosa, A:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Natl Inst Hlth Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

Ortega, G:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Natl Inst Hlth Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

Sanabria, A:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Natl Inst Hlth Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

Perez-Cordon, A:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

Canabate, P:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Natl Inst Hlth Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

Moreno, M:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Preckler, S:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Ruiz, S:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Natl Inst Hlth Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

Aguilera, N:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Pineda, JA:
 Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, Seville, Spain

Macias, J:
 Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, Seville, Spain

Alarcon-Martin, E:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Univ Malaga, Sch Med, Dept Surg Biochem & Mol Biol, Malaga, Spain

Sotolongo-Grau, O:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Marquie, M:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Monte-Rubio, G:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Valero, S:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Natl Inst Hlth Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

Benaque, A:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Clarimon, J:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Memory Unit, Neurol Dept, Barcelona, Spain

 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, Barcelona, Spain

Bullido, MJ:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severn Ochoa, Madrid, Spain

 Inst Invest Sanitaria Hosp La Paz IdiPaz, Madrid, Spain

Garcia-Ribas, G:
 Hosp Univ Ramon y Cajal, Madrid, Spain

 Inst Salud Carlos III, Madrid, Spain

Pastor, P:
 Fundacio Recerca Biomed & Social Mutua Terrassa, Terrassa, Spain

 Univ Barcelona, Hosp Univ Mutua Terrassa, Dept Neurol, Sch Med,Memory Disorders Unit, Terrassa, Spain

 Fundacio Recerca Biomed & Social Mutua Terrassa, Barcelona, Spain

 Univ Barcelona, Sch Med, Hosp Mutua Terrassa, Memory Disorders Unit,Dept Neurol, Barcelona, Spain

Sanchez-Juan, P:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Cantabria, Neurol Serv, Marques de Valdecilla Univ Hosp, Santander, Spain

 IDIVAL, Santander, Spain

Alvarez, V:
 Hosp Univ Cent Asturias, Lab Genet, Oviedo, Spain

 Inst Invest Biosanit Principado Asturias ISPA, Oviedo, Spain

Pinol-Ripoll, G:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Hosp Univ Santa Maria Lleida, Inst Recerca Biomed Lleida IRBLLeida, Unitat Trastorns Cognitius, Lleida, Spain

Garcia-Alberca, JM:
 Andalusian Inst Neurosci, Alzheimer Res Ctr, Malaga, Spain

 Andalusian Inst Neurosci, Memory Clin, Malaga, Spain

Royo, JL:
 Univ Malaga, Sch Med, Dept Surg Biochem & Mol Biol, Malaga, Spain

Franco, E:
 Univ Seville, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBiS, Unidad Demencias,Serv Neurol & Neurofisiol, Seville, Spain

Mir, P:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Seville, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBiS, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

Calero, M:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Queen Sofia Fdn Alzheimer Ctr, CIEN Fdn, Madrid, Spain

 Inst Salud Carlos III, Madrid, Spain

Medina, M:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Inst Invest Sanitaria Hosp La Paz IdiPaz, Madrid, Spain

 Queen Sofia Fdn Alzheimer Ctr, CIEN Fdn, Madrid, Spain

Rabano, A:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Queen Sofia Fdn Alzheimer Ctr, CIEN Fdn, Madrid, Spain

 BT CIEN, Madrid, Spain

Avila, J:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 UAM, CSIC, CBMSO, Dept Mol Neuropathol, Madrid, Spain

Antunez, C:
 Hosp Clin Univ Virgen de la Arrixaca, Unidad Demencias, Murcia, Spain

Real, LM:
 Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, Seville, Spain

 Univ Malaga, Sch Med, Dept Surg Biochem & Mol Biol, Malaga, Spain

Orellana, A:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Carracedo, A:
 Univ Santiago de Compostela, Grp Med Xenom, Ctr Nacl Genotipado CEGEN, PRB3,ISCIII, Santiago De Compostela, Spain

 Fdn Publ Galega Med Xenom, CIBERER IDIS, Santiago De Compostela, Spain

Saez, ME:
 Ctr Andaluz Estudios Bioinformat, CAEBI, Seville, Spain

Tarraga, L:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Natl Inst Hlth Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

Boada, M:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Natl Inst Hlth Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

Ruiz, A:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Natl Inst Hlth Carlos III, Minist Econ & Competitiveness, CIBERNED, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

Alarcon, E:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Univ Malaga, Sch Med, Dept Surg Biochem & Mol Biol, Malaga, Spain

Buendia, M:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Corbaton, A:
 Hosp Clin San Carlos, CIBERDEM, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain

Diego, S:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Gailhajenet, A:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Gonzalez, PG:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Guitart, M:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Ibarria, M:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Martin, E:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

 Univ Malaga, Sch Med, Dept Surg Biochem & Mol Biol, Malaga, Spain

Martinez, MT:
 Hosp Clin San Carlos, CIBERDEM, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain

Pancho, A:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Peleja, E:
 Univ Int Catalunya, Res Ctr & Memory Clin Fundacio ACE, Inst Catala Neurociencies Aplicades, Barcelona, Spain

Pineda, JA:
 Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, Seville, Spain

Real, LM:
 Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, Seville, Spain

 Univ Malaga, Sch Med, Dept Surg Biochem & Mol Biol, Malaga, Spain

Serrano-Rios, M:
 Hosp Clin San Carlos, CIBERDEM, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain

Adarmes-Gomez, AD:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Seville, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBiS, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

Alvarez, I:
 Fundacio Recerca Biomed & Social Mutua Terrassa, Barcelona, Spain

 Univ Barcelona, Sch Med, Hosp Mutua Terrassa, Memory Disorders Unit,Dept Neurol, Barcelona, Spain

Amer-Ferrer, G:
 Hosp Univ Son Espases, Dept Neurol, Palma De Mallorca, Spain

Antequera, M:
 Hosp Clin Univ Virgen de la Arrixaca, Unidad Demencias, Murcia, Spain

Baquero, M:
 Hosp Univ & Politecn La Fe, Servei Neurol, Valencia, Spain

Bernal, M:
 Univ Seville, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBiS, Unidad Demencias,Serv Neurol & Neurofisiol, Seville, Spain

Blesa, R:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Memory Unit, Neurol Dept, Barcelona, Spain

 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, Barcelona, Spain

Buiza-Rueda, D:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Seville, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBiS, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

Bullido, MJ:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severn Ochoa, Madrid, Spain

 Inst Invest Sanitaria Hosp La Paz IdiPaz, Madrid, Spain

Burguera, JA:
 Hosp Univ & Politecn La Fe, Servei Neurol, Valencia, Spain

Carrillo, F:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Seville, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBiS, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

Carrion-Claro, M:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Seville, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBiS, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

Casajeros, MJ:
 Hosp Univ Ramon y Cajal, Madrid, Spain

Cruz-Gamero, JM:
 Univ Malaga, Sch Med, Dept Surg Biochem & Mol Biol, Malaga, Spain

de Pancorbo, MM:
 BIOMICs, Pais Vasco, Spain

 Univ Basque Country, UPV EHU, Ctr Invest Lascaray, Bilbao, Spain

del Ser, T:
 Inst Invest Sanitaria Hosp La Paz IdiPaz, Madrid, Spain

Diez-Fairen, M:
 Fundacio Recerca Biomed & Social Mutua Terrassa, Barcelona, Spain

 Univ Barcelona, Sch Med, Hosp Mutua Terrassa, Memory Disorders Unit,Dept Neurol, Barcelona, Spain

Fortea, J:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Memory Unit, Neurol Dept, Barcelona, Spain

 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, Barcelona, Spain

Frank-Garcia, A:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Inst Invest Sanitaria Hosp La Paz IdiPaz, Madrid, Spain

 Hosp Univ La Paz UAM, Neurol Serv, Madrid, Spain

Madrona, SG:
 Inst Salud Carlos III, Madrid, Spain

Gomez-Garre, P:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Seville, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBiS, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

Hevilla, S:
 Andalusian Inst Neurosci, Alzheimer Res Ctr, Malaga, Spain

 Andalusian Inst Neurosci, Memory Clin, Malaga, Spain

Jesus, S:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Seville, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBiS, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

Espinosa, MAL:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Seville, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBiS, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

Lage, C:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Cantabria, Neurol Serv, Marques de Valdecilla Univ Hosp, Santander, Spain

 IDIVAL, Santander, Spain

Legaz, A:
 Hosp Clin Univ Virgen de la Arrixaca, Unidad Demencias, Murcia, Spain

Lleo, A:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Memory Unit, Neurol Dept, Barcelona, Spain

 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, Barcelona, Spain

de Munain, AL:
 Hosp Donostia San Sebastian, Donostia San Sebastian, Gipuzkoa, Spain

Lopez-Garcia, S:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Cantabria, Neurol Serv, Marques de Valdecilla Univ Hosp, Santander, Spain

 IDIVAL, Santander, Spain

Macias, D:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Seville, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBiS, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

Manzanares, S:
 Hosp Clin Univ Virgen de la Arrixaca, Unidad Demencias, Murcia, Spain

 Fdn Formac & Invest Sanitarias Reg Murcia, Murcia, Spain

Marin, M:
 Univ Seville, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBiS, Unidad Demencias,Serv Neurol & Neurofisiol, Seville, Spain

Marin-Munoz, J:
 Hosp Clin Univ Virgen de la Arrixaca, Unidad Demencias, Murcia, Spain

Marin, T:
 Andalusian Inst Neurosci, Alzheimer Res Ctr, Malaga, Spain

 Andalusian Inst Neurosci, Memory Clin, Malaga, Spain

Montes, AM:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severn Ochoa, Madrid, Spain

 Hosp Univ La Paz UAM, Neurol Serv, Madrid, Spain

Martinez, B:
 Hosp Clin Univ Virgen de la Arrixaca, Unidad Demencias, Murcia, Spain

Martinez, C:
 Inst Invest Biosanit Principado Asturias ISPA, Oviedo, Spain

 Hosp Cabuenes Gijon, Serv Neurol, Gijon, Spain

Martinez, V:
 Hosp Clin Univ Virgen de la Arrixaca, Unidad Demencias, Murcia, Spain

Alvarez, PML:
 Fdn CITA Alzheimer, Ctr Invest & Terapias Avanzadas, Donostia San Sebastian, Gipuzkoa, Spain

Iriarte, MM:
 Navarrabiomed, Pamplona, Spain

Menendez-Gonzalez, M:
 Inst Invest Biosanit Principado Asturias ISPA, Oviedo, Spain

 Hosp Univ Cent Asturias, Serv Neurol, Oviedo, Spain

Molinuevo, JL:
 Fundacio Pasqual Maragall, Barcelona Brain Res Ctr, Barcelona, Spain

Pastor, AB:
 Queen Sofia Fdn Alzheimer Ctr, CIEN Fdn, Madrid, Spain

Tur, JP:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Inst Biomed Valencia, CSIC, Unitat Genet Mol, Valencia, Spain

 Inst Invest Sanitaria La Fe, Unidad Mixta Neurol Genet, Valencia, Spain

Perinan-Tocino, T:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Seville, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBiS, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

de Asua, DR:
 Hosp Univ La Princes, Madrid, Spain

Rodrigo, S:
 Univ Seville, Hosp Univ Virgen del Rocio, CSIC,Inst Biomed Sevilla IBiS, Unidad Demencias,Serv Neurol & Neurofisiol, Seville, Spain

Rodriguez-Rodriguez, E:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Cantabria, Neurol Serv, Marques de Valdecilla Univ Hosp, Santander, Spain

 IDIVAL, Santander, Spain

Diaz, RSD:
 Hosp Clin Barcelona, Barcelona, Spain

Sastre, E:
 Natl Inst Hlth Carlos III, CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severn Ochoa, Madrid, Spain

Vicente, MP:
 Hosp Clin Univ Virgen de la Arrixaca, Unidad Demencias, Murcia, Spain

Vivancos, L:
 Hosp Clin Univ Virgen de la Arrixaca, Unidad Demencias, Murcia, Spain
ISSN: 15525260
Editorial
WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Estados Unidos America
Tipo de documento: Article
Volumen: 15 Número: 10
Páginas: 1333-1347
WOS Id: 000490148500009
ID de PubMed: 31473137
imagen Green Published, Green Accepted, Hybrid Gold

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