Genetic dissection of hippocampal sclerosis of ageing using magnetic resonance imaging surrogates
Olive, C.; De Rojas, I.; Zhang, L.; Sotolongo-Grau, O.; Quintela, I.; Garcia-Gonzalez, P.; Puerta Fuentes, R.; Garcia-Gutierrez, F.; Montrreal, L.; Capdevila-Bayo, M.; Miguel, A.; Blazquez-Folch, J.; Calero, M.; Rabano, A.; Belen Pastor, A.; del Ser, T.; Medina, M.; Carracedo, A.; Ramirez, A.; Molina-Porcel, L.; Tarrega, L.; Cano, A.; Valero, S.; Marquie, M.; Sanchez-Juan, P.; Boada, M.; Strange, B.; Fernandez, M. V.; Ruiz, A.
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INTRODUCTIONHippocampal sclerosis of aging (HS-aging) is frequently present in individuals over 85 who die with dementia. Recent studies suggest that some loci associated with Alzheimers disease (AD) may be more related to HS-aging. We aimed to find AD-associated SNPs potentially related to HS-aging. METHODSWe assessed the relation of the AD polygenic risk score (AD-PRS) with hippocampal subfield volumes assessed by magnetic resonance imaging (MRI) as HS-by-proxy in 1,130 non-demented participants. We analyzed 1,708 individuals to associate their AD-PRS (83 variants) with AD alongside HS-aging. RESULTSHS-by-proxy measures of fimbria and hippocampal body and head show association with AD-PRS, SHARPIN, GRN and TNIP1, also after replication. We replicated the stronger AD-PRS association with AD in the presence of HS-aging compared to AD alone. DISCUSSIONResults show association between some AD-SNPs and HS-proxy, enriched in immune-brain axis pathways, differentiating HS-aging from AD. This insight aids in understanding their interrelationships and identifying specific therapeutic targets.
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