Alzheimer's disease (AD) and Frontotemporal dementia (FTD): investigating the overlap of genetic mutations focusing on CD33 and TREM2
| Autor: | A. Rendina S. Napoletano G. Milan L. Fucci E. Vitale. |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | SIB 2017 59° Congress, Caserta, Italy, 20-22 September 2017 info:cnr-pdr/source/autori:A. Rendina S. Napoletano G. Milan L. Fucci E. Vitale./congresso_nome:SIB 2017 59° Congress,/congresso_luogo:Caserta, Italy/congresso_data:20-22 September 2017/anno:2017/pagina_da:/pagina_a:/intervallo_pagine |
| Popis: | Frontotemporal dementia (FTD) and Alzheimer's disease (AD) are two complex neurodegenerative disorders with associated several genes thus suggesting that a common molecular pathway could exist and is yet unknown. Despite massive research and drug development, there are still no therapies that slow down or stop their progression. Mutations in genes related to neuroinflammation, including CD33 and TREM2, may be risk factors and could be entry points for therapeutic intervention. Two CD33 SNPs and one in TREM2 were described to be predisposing factors to Late Onset Alzheimer disease (LOAD). In particular, CD33 SNPs rs3865444 and rs12459419 in minor alleles were found to confer strong protection while conferring elevated risk of LOAD in major alleles. These SNPs directly modulate CD33 exon 2 splicing efficiency. Moreover, the rare heterozygous missense variant rs75932628-T in TREM2 exon 2 was strongly associated with the capacity of TREM2 to activate microglial cells. In order to assess the presence of these polymorphisms in our cohort, we analyzed 216 Caucasians diagnosed with LOAD and 50 healthy controls. We performed High Resolution Melting analysis (HRM) on genomic DNA from whole blood of the patients and we sequenced by Sanger method individuals showing different melting curves and we used these results as reference in our analysis. Our patients exhibited the coinheritance of SNPs rs12459419 and rs3865444. In addition, we identified a third SNP in CD33 exon 2, rs2455069, which belongs to a previously identified LD SNP block associated with an increased rate of cognitive decline. We found that all patients analyzed for SNP rs75932628 in TREM2 gene are homozygous for the wild-type allele. However, some individuals are heterozygous for the nearby SNP rs143332484, which could be potentially associated with AD in our population. Further investigations are in progress to understand the mechanism of action of these two genes. |
| Databáze: | OpenAIRE |
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