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Articles by Richard Einstein
Total Records ( 3 ) for Richard Einstein
  Margaret A. Calciano , Weiyin Zhou , Peter J. Snyder and Richard Einstein
  Background: Increasing cholinergic activity has been the primary mechanism for treating dementia due to Alzheimer’s disease. However, the effectiveness of cholinesterase inhibitors (ChEIs) is still widely debated. The identification of specific biomarkers capable of identifying patients more likely to respond to these treatments could potentially provide specific evidence to clearly address this controversy through patient stratification. The goal of this study was to determine the feasibility of discovering biomarkers specific for the treatment of Alzheimer’s disease. Methods: Peripheral blood was collected from a cohort of patients treated with different ChEIs. Total RNA was isolated and profiled on the human Genome-Wide SpliceArray (GWSA) to test the feasibility of discriminating the different treatment subgroups of subjects based on the expression patterns generated from the Genome-Wide SpliceArray. Results: Specific expression differences were identified for the various treatment groups that lead to a clear separation between patients treated with ChEIs versus naïve patients when Principal Component Analysis was performed on probe sets selected for differential expression. In addition, specific probe sets were identified to be dependent on the inhibitor used among the treated patients. Conclusions: Distinct separation between non-treated, galantamine, donepezil, and rivastigmine-treated patients was clearly identified based on small sets of expression probes. The ability to identify drug-specific treatment expression differences strengthens the potential for using peripheral gene signatures for the identification of individuals responding to drug treatment.
  Pascale Fehlbaum- Beurdeley , Anne Charlotte Jarrige-Le Prado , Diego Pallares , Jennifer Carriere , Caroline Guihal , Cyril Soucaille , Fabien Rouet , Dominique Drouin , Olivier Sol , Heather Jordan , Darong Wu , Ling Lei , Richard Einstein , Fabien Schweighoffer and Laurent Bracco
  Background There is a significant need for reliable molecular biomarkers to aid in Alzheimer's disease (AD) clinical diagnosis. Methods We performed a genome-wide investigation of the human transcriptome, taking into account the discriminatory power of splice variations from the blood of 80 AD patients and 70 nondemented control (NDC) individuals. Results We characterized a blood RNA signature composed of 170 oligonucleotide probe sets associated with 133 genes that can correctly distinguish AD patients from NDC with a sensitivity of 100% and specificity of 96%. Functionally, this signature highlights genes involved in pathways that were associated with macrophages and lymphocytes within AD patients: Transforming growth factor (TGF-β) signaling, oxidative stress, innate immunity and inflammation, cholesterol homeostasis, and lipid-raft perturbation, whereas other genes may also provide new insights in the biology of AD. Conclusions This study provides proof-of-concept that whole-blood profiling can generate an AD-associated classification signature via the specific relative expression of biologically relevant RNAs. Such a signature will need to be validated with extended patient cohorts, and evaluated to learn whether it can differentiate AD from others types of dementia.
  Zaven S. Khachaturian , Deborah Barnes , Richard Einstein , Sterling Johnson , Virginia Lee , Allen Roses , Mark A. Sager , William R. Shankle , Peter J. Snyder , Ronald C. Petersen , Gerard Schellenberg , John Trojanowski , Paul Aisen , Marilyn S. Albert , John C.S. Breitner , Neil Buckholtz , Maria Carrillo , Steven Ferris , Barry D. Greenberg , Michael Grundman , Ara S. Khachaturian , Lewis H. Kuller , Oscar L. Lopez , Paul Maruff , Richard C. Mohs , Marcelle Morrison- Bogorad , Creighton Phelps , Eric Reiman , Marwan Sabbagh , Mary Sano , Lon S. Schneider , Eric Siemers , Pierre Tariot , Jacques Touchon , Bruno Vellas and Lisa J. Bain
  Among the major impediments to the design of clinical trials for the prevention of Alzheimer's disease (AD), the most critical is the lack of validated biomarkers, assessment tools, and algorithms that would facilitate identification of asymptomatic individuals with elevated risk who might be recruited as study volunteers. Thus, the Leon Thal Symposium 2009 (LTS'09), on October 27–28, 2009 in Las Vegas, Nevada, was convened to explore strategies to surmount the barriers in designing a multisite, comparative study to evaluate and validate various approaches for detecting and selecting asymptomatic people at risk for cognitive disorders/dementia. The deliberations of LTS'09 included presentations and reviews of different approaches (algorithms, biomarkers, or measures) for identifying asymptomatic individuals at elevated risk for AD who would be candidates for longitudinal or prevention studies. The key nested recommendations of LTS'09 included: (1) establishment of a National Database for Longitudinal Studies as a shared research core resource; (2) launch of a large collaborative study that will compare multiple screening approaches and biomarkers to determine the best method for identifying asymptomatic people at risk for AD; (3) initiation of a Global Database that extends the concept of the National Database for Longitudinal Studies for longitudinal studies beyond the United States; and (4) development of an educational campaign that will address public misconceptions about AD and promote healthy brain aging.
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