Publications by authors named "Maria Carolina Dalmasso"

5 Publications

  • Page 1 of 1

A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

Acta Neuropathol 2019 08 27;138(2):237-250. Epub 2019 May 27.

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.

The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00401-019-02026-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660501PMC
August 2019

Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer's disease.

Transl Psychiatry 2019 01 31;9(1):55. Epub 2019 Jan 31.

NEUROFARBA (Department of Neuroscience, Psychology, Drug Research and Child Health), University of Florence, Florence, Italy.

Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer's disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-019-0394-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355764PMC
January 2019

Identification of PSEN2 mutation p.N141I in Argentine pedigrees with early-onset familial Alzheimer's disease.

Neurobiol Aging 2015 Oct 15;36(10):2674-7.e1. Epub 2015 Jun 15.

Laboratorio de Bioquímica Molecular, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina; Centro de Neuropsiquiatria y Neurología de la Conducta (CENECON), Departamento Ciencias Fisiológicas UAII, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina. Electronic address:

Presenilin 2 gene (PSEN2) mutations account for <5% of all early-onset familial Alzheimer's disease (EOFAD) cases and only 13 have strong evidence for pathogenicity. We aimed to investigate the presence of PSEN2 mutation p.N141I and characterize the clinical phenotypes in 2 Argentine pedigrees (AR2 and AR3) with clinical symptoms of EOFAD. Detailed clinical assessments and genetic screening for PSEN2 and APOE genes were carried out in 19 individuals of AR2 and AR3 families. The p.N141I mutation was identified in all affected subjects and was associated with prominent early onset, rapidly progressive dementia, neurologic, and behavioral symptoms. AR2 and AR3 families share the same Volga German ancestry as all the families reported presenting this mutation. To our knowledge, this is the first report of PSEN2 mutation p.N141I in Argentina and even more, in South America. Our contribution increases the total number of described families carrying this mutation and help to improve the characterization of clinical phenotype in EOFAD associated to PSEN2 mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurobiolaging.2015.06.011DOI Listing
October 2015

Canonical and variant histones of protozoan parasites.

Front Biosci (Landmark Ed) 2011 Jun 1;16:2086-105. Epub 2011 Jun 1.

Laboratorio de Parasitologia Molecular, Instituto de Investigaciones Biotecnologicas-Instituto Tecnologico Chascomus (IIB-INTECH), UNSAM-CONICET, Chascomus 7130, Argentina.

Protozoan parasites have tremendously diverse lifestyles that require adaptation to a remarkable assortment of different environmental conditions. In order to complete their life cycles, protozoan parasites rely on fine-tuning gene expression. In general, protozoa use novel regulatory elements, transcription factors, and epigenetic mechanisms to regulate their transcriptomes. One of the most surprising findings includes the nature of their histones--these primitive eukaryotes lack some histones yet harbor novel histone variants of unknown function. In this review, we describe the histone components of different protozoan parasites based on literature and database searching. We summarize the key discoveries regarding histones and histone variants and their impact on chromatin regulation in protozoan parasites. In addition, we list histone genes IDs, sequences, and genomic localization of several protozoan parasites and Microsporidia histones, obtained from a thorough search of genome databases. We then compare these findings with those observed in higher eukaryotes, allowing us to highlight some novel aspects of epigenetic regulation in protists and to propose questions to be addressed in the upcoming years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2741/3841DOI Listing
June 2011