Director of the Alzheimer‘s Disease and Memory Disorders Center
Alzheimer Disease / Memory Disorders; Neurology
I am a board-certified neurologist with specialty training in genetics and cognitive disorders, and I direct the Alzheimer’s Disease and Memory Disorders Center and Translational Genomics Research Laboratory, state-of-the-art facilities specializing in cognitive disorders.
Our clinical mission is to provide compassionate, state-of-the-art care for patients and families affected by Alzheimer disease (AD) and other cognitive disorders. Our multidisciplinary approach includes a team of neurologists, neuropsychologists, neuroimagers, social workers and nurses dedicated to the needs of our patients and their caregivers.
Our research mission is to employ genetic tools to identify novel risk factors and potential pathways that can be targeted with medications to prevent or modify the course of AD. Our focus is translating discoveries made in the laboratory into improved methods of disease prevention, diagnosis, and treatment.
AD is a progressive neurodegenerative disease with high prevalence imposing a substantial public health problem. The heritability of AD is estimated at 60-80 %, forecasting a potential for using genetic biomarkers for risk stratification in the future. The main risk factor of late-onset AD is the APOE4 allele with a population attributable fraction of 0.2-0.3. Several large scale genome-wide association studies (GWAS) using high frequency variants identified nine additional loci with a combined population attributable fraction of 0.31. My laboratory focuses on finding the missing heritability using copy number variation as a genetic marker map. We perform CNV GWAS analysis on case-control datasets and quantitative endophenotypes, such as age at onset and biomarker data.
We identified an olfactory receptor CNV association with age at onset of AD. Loss of smell sensation has been associated with AD and other neurodegenerative disorders; we are now applying a novel method, aCGH to study the olfactory subgenome in relation to smell sensation and cognition in normal aging individuals, patients affected by amnestic mild cognitive impairment and mild AD. This multicenter study is ongoing and is funded by the National Institute of Aging.
In order to increase the power of association studies, we developed a method to use CNV as a genetic marker map and whole genome gene expression as quantitative trait loci within the same individual using post-mortem human temporal lobe tissue. In a pilot study, we identified a replicable 8 kb deletion association with AD upstream of CREB1. This small deletion harbors a PAX6 transcription factor binding site. We are pursuing iPSC technology to study the effect of this deletion on human neurons. We are also applying the same methodology on a larger set to identify additional signals.
Our laboratory also collaborates with the Mendelian Project of Baylor College of Medicine in Houston, Texas. We are studying neurodegenerative dementias with Mendelian inheritance pattern by whole exome sequencing of informative pedigrees. My laboratory performs the data analysis and the follow-up studies for these mutations.