INVESTIGADORES
GALEANO Pablo
artículos
Título:
NEW INSIGHTS INTO THE GENETIC ETIOLOGY OF ALZHEIMER'S DISEASE AND RELATED DEMENTIAS
Autor/es:
BELLENGUEZ, CÉLINE; KUCUKALI, FAHRI; JANSEN, IRIS; KLEINEIDAM, LUCAS; MORENO-GRAU, SONIA; MORELLI, LAURA; GALEANO, PABLO (COLLABORATOR); NOVACK, GISELA VANINA (COLLABORATOR); PRESTIA, FEDERICO ARIEL (COLLABORATOR); CASTAÑO, EDUARDO (COLLABORATOR); RUIZ, AGUSTÍN; RAMIREZ, ALFREDO; LAMBERT, JEAN-CHARLES; MÁS DE 2OO AUTORES Y COLABORADORES (NO ES POSIBLE CARGARLOS)
Revista:
NATURE GENETICS
Editorial:
NATURE PUBLISHING GROUP
Referencias:
Lugar: Londres; Año: 2022 vol. 54 p. 412 - 436
ISSN:
1061-4036
Resumen:
Characterization of the genetic landscape of Alzheimers disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two stage genome-wide association study totaling 111326 clinically diagnosed proxy AD cases and 677663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD dementia or progression from mild cognitive impairment to AD dementia. The improvement in prediction led to a 1.6 to 1.9 fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE e4 allele.