The MAPT H1 Haplotype Is a Risk Factor for Alzheimer's Disease in APOE epsilon 4 Non-carriers


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

Publicada: 4 dic 2019
Resumen:
An ancestral inversion of 900 kb on chromosome 17q21, which includes the microtubule-associated protein tau (MAPT) gene, defines two haplotype clades in Caucasians (H1 and H2). The H1 haplotype has been linked inconsistently with AD. In a previous study, we showed that an SNP tagging this haplotype (rs1800547) was associated with AD risk in a large population from the Dementia Genetics Spanish Consortium (DEGESCO) including 4435 cases and 6147 controls. The association was mainly driven by individuals that were non-carriers of the APOE epsilon 4 allele. Our aim was to replicate our previous findings in an independent sample of 4124 AD cases and 3290 controls from Spain (GR@ACE project) and to analyze the effect of the H1 sub-haplotype structure on the risk of AD. The H1 haplotype was associated with AD risk (OR = 1.12; p = 0.0025). Stratification analysis showed that this association was mainly driven by the APOE epsilon 4 non-carriers (OR = 1.15; p = 0.0022). Pooled analysis of both Spanish datasets (n = 17,996) showed that the highest AD risk related to the MAPT H1/H2 haplotype was in those individuals that were the oldest [third tertile (>77 years)] and did not carry APOE epsilon 4 allele (p = 0.001). We did not find a significant association between H1 sub-haplotypes and AD. H1c was nominally associated but lost statistical significance after adjusting by population sub-structure. Our results are consistent with the hypothesis that genetic variants linked to the MAPT H1/H2 are tracking a genuine risk allele for AD. The fact that this association is stronger in APOE epsilon 4 non-carriers partially explains previous controversial results and might be related to a slower alternative causal pathway less dependent on brain amyloid load.

Filiaciones:
Sanchez-Juan, P:
 Minist Econ & Competitiveness, Natl Inst Hlth Carlos III, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

de Rojaso, I:
 Minist Econ & Competitiveness, Natl Inst Hlth Carlos III, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

Lopez-Garcia, S:
 Minist Econ & Competitiveness, Natl Inst Hlth Carlos III, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

Rodriiguez-Rodriguez, E:
 Minist Econ & Competitiveness, Natl Inst Hlth Carlos III, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

Moreno-Grau, S:
 Minist Econ & Competitiveness, Natl Inst Hlth Carlos III, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

Rodriguez-Gomez, O:
 Minist Econ & Competitiveness, Natl Inst Hlth Carlos III, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

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

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

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

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

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

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

 Andalusian Inst Neurosci, Alzheimer Res Ctr, Malaga, Spain

 Andalusian Inst Neurosci, Memory Clin, Malaga, Spain

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

Perez, AG:
 Ctr Andaluz Estudios Bioinformat, Seville, Spain

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

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

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

Adarmes-Gomez, AD:
 Univ Seville, CSIC, Hosp Univ Virgen del Rocio,Inst Biomed Sevilla, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

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

Buiza-Rueda, D:
 Univ Seville, CSIC, Hosp Univ Virgen del Rocio,Inst Biomed Sevilla, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

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

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

Carrion-Claro, M:
 Univ Seville, CSIC, Hosp Univ Virgen del Rocio,Inst Biomed Sevilla, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

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

Gomez-Garre, P:
 Univ Seville, CSIC, Hosp Univ Virgen del Rocio,Inst Biomed Sevilla, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

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

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

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

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

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

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

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

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

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

Perinan-Tocino, T:
 Univ Seville, CSIC, Hosp Univ Virgen del Rocio,Inst Biomed Sevilla, Unidad Trastornos Movimiento,Serv Neurol & Neurof, Seville, Spain

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

Blesa, R:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, St Pau Memory Unit,Neurol Dept, Barcelona, Spain

Bullido, MJ:
 Inst Invest Sanitaria Hosp la Paz, Madrid, Spain

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

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

 Inst Salud Carlos III, Madrid, Spain

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

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

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

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

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

 Inst Invest Sanitaria Hosp la Paz, Madrid, Spain

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

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

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

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

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

Lopez-Garcia, S:
 Minist Econ & Competitiveness, Natl Inst Hlth Carlos III, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

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

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

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

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

 Inst Invest Sanitaria Hosp la Paz, Madrid, Spain

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

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

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

Ripoll, GP:
 Natl Inst Hlth Carlos III, Network Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain

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

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

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

 BT CIEN, Madrid, Spain

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

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

Sanchez-Juan, P:
 Minist Econ & Competitiveness, Natl Inst Hlth Carlos III, Ctr Networked Biomed Res Neurodegenerat Dis, Madrid, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Res Ctr, Barcelona, Spain

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

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

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

Alarcon-Martin, E:
 Univ Malaga, Sch Med, Dept Surg Biochem & Mol Biol, Malaga, Spain

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

 Univ Int Catalunya, Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain

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

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

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

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

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

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

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

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

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

 Inst Invest Biosanit Principado Asturias, Oviedo, Spain

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

 Hosp Cabuenes, Serv Neurol, Gijon, Spain

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

 Hosp Univ Cent Asturias, Serv Neurol, Oviedo, 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

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

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

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

 Fdn Formac & Invest Sanitarias Reg Murcia, Murcia, Spain

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

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

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

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

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

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

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

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

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

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

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

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

Garcia-Ribas, G:
 Inst Salud Carlos III, Madrid, Spain

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

de Pancorbo, MM:
 Univ Basque Country, UPV EHU, Ctr Invest Lascaray, BIOMICs, Leioa, Spain

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

 Andalusian Inst Neurosci, Memory Clin, Malaga, Spain

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

 Andalusian Inst Neurosci, Memory Clin, Malaga, Spain

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

 Andalusian Inst Neurosci, Memory Clin, Malaga, Spain

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

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

Iriarte, MM:
 Navarrabiomed, Pamplona, Spain

Molinuevo, JL:
 Fundacio Pasqua Maragall, Barcelonasseta Brain Res Ctr, Barcelona, Spain

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

Diaz, RSD:
 Hosp Clin Barcelona, Barcelona, Spain
ISSN: 16634365





Frontiers in Aging Neuroscience
Editorial
FRONTIERS MEDIA SA, AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND, Suiza
Tipo de documento: Article
Volumen: 11 Número:
Páginas:
WOS Id: 000503234400001
ID de PubMed: 31866851
imagen Green Published, gold

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