Alzheimer’s Disease Endophenotypes Genetics

Recent genetic studies of complex traits and diseases have focused on the identification of common variants associated with risk through genome-wide association studies (GWAS).

In this study, we will use GWAS and sequence data data to identify variants, genes and pathways associated with cerebrospinal fluid levels of known AD biomarkers (tau, ptau, Aβ, YKL40, VILIP1) and other AD-related proteins (CLU, APOE, TREM2), and other AD-related endophenotypes

The Familial Alzheimer’s Sequencing (FASe) project

The aim of this research is to identify rare functional variants with large effect size on risk for Alzheimer’s disease (AD).

We hypothesize that families with extensive history of dementia are enriched for genetic risk factors and that by sequencing those families, we will identify rare variants with large effect size. In this project, we will combine sequencing data in families with late-onset AD and genotyping data in large case-control series….

Brain Transcriptomics

Genetic variants in several genes that lead to AD were identified more than 20 years ago. However, the processes disrupted by the expression of those variants are still not totally understood.

The pathogenic events in the brain that lead to Alzheimer’s disease are the result of multifactorial genetic and biological changes that, in turn, causes pleiotropic changes in molecular networks linking a host of biological processes, resulting in disease…

High throughput Proteomics

Proteins levels play important roles in numerous biological pathways, contribute to risk for many diseases, and have been widely used for clinical risk assessment, diagnosis, prognosis and evaluation of treatment efficacy.

When used as quantitative traits in genetic studies they can act as intermediate phenotypes that functionally relate genetic variation to disease-predisposing factors and then to complex disease end-points. We are generating and analyzing …

Parkinson Disease Genomics

Cognitive impairment is an important symptom of Parkinson’s disease (PD) progression; dementia is present in 80% of patients in long-term PD studies.

PD is characterized by protein misfolding and aggregation. We are using quantitative endophenotypes such as cerebrospinal fluid levels for α-synuclein,  neuroimaging or clinical longitudinal data to identify novel genes and pathways associated with Parkinson’s disease risk, onset or….

Stroke Genetics

Stroke is the 2nd leading cause of death throughout the world, and the leading cause of long-term disability.

In the first hours after stroke onset, neurological deficits can be highly unstable, with many patients improving while others deteriorate. These early changes have a major impact on long-term outcome. The goal of this research is to identify genetic variants associated with early neurological outcome after Ischemic stroke …

Genetic Overlap across Neurodegeneration

Aging populations worldwide, and particularly developed countries, face an increasing burden of neurodegenerative diseases. Cognitive impairment is the most prominent in Alzheimer’s disease (AD) and in Frontotemporal dementia (FTD), but it is also an important feature of Parkinson’s disease (PD) (dementia is present in 80% of patients in studies of long-term follow up).

The goal of this study is to use genome-wide association data, exome chip data and whole genome/exome sequence data to genes and pathways in common between these neurodegenerative diseases..

Multi-Omic and Functional Genomics in Neurodegenerative Diseases

Most of neurodegenerative cases present a complex genetic architecture, in which many genes and pathways are associated the etiology of diseases, and  downstream effects of genetic variants can affect a myriad of factors in biological networks, including transcriptomic, proteomic, epigenomic, among others, that could converge into disease. 

The analysis of data sets with several omics assays can reveal novel mechanistic insights, otherwise missed in omic-specific analyses…