2026-05-20T03:47:19Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/227212025-05-08T10:50:01Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967col_20.500.12105_16970

00925njm 22002777a 4500 dc Sánchez-Juan, Pascual author Moreno, Sonia author de Rojas, Itziar author Hernandez, Isabel author Valero, Sergi author Alegret, Montse author Montrreal, Laura author Garcia Gonzalez, Pablo author Lage, Carmen author Lopez-Garcia, Sara author Rodriiguez-Rodriguez, Eloy author Orellana, Adelina author Tarraga, Lluis author Boada, Merce author Ruiz, Agustin author GR@ACE Study Group author DEGESCO Consortium author 2019-12-04 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. Sanchez-Juan P, Moreno S, De Rojaso I, Hernandez I, Valero S, Alegret M, et al. The MAPT H1 Haplotype Is a Risk Factor for Alzheimer's Disease in APOE epsilon 4 Non-carriers. Front Aging Neurosci. 2019 Dec 04;11:327. 10.3389/fnagi.2019.00327 1663-4365 Frontiers in Aging Neuroscience http://hdl.handle.net/20.500.13003/12631 31866851 L630230975 2-s2.0-85077263835 https://hdl.handle.net/20.500.12105/22721 503234400001 Alzheimer's disease MAPT APOE genetic association The MAPT H1 Haplotype Is a Risk Factor for Alzheimer's Disease in APOE epsilon 4 Non-carriers