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Donna Crenshaw

Donna Crenshaw

Assistant Professor of Pathology
Pathology
donna.crenshaw@duke.edu
DUMC 2927, Durham, NC 27710
Room 127 Davison Building, DUMC 2927, Durham, NC 27710

Selected Publications

New Genetic Approaches to AD: Lessons from APOE-TOMM40 Phylogenetics.

Journal Article Curr Neurol Neurosci Rep · May 2016 Clinical trials for Alzheimer's disease are now focusing on the earliest stages of the disease with the goal of delaying dementia onset. There is great utility in using genetic variants to identify individuals at high age-dependent risk when the goal is to ... Full text Link to item Cite

Effects of low doses of pioglitazone on resting-state functional connectivity in conscious rat brain.

Journal Article PLoS One · 2015 Pioglitazone (PIO) is a peroxisome proliferator-activated receptor-γ (PPARγ) agonist in clinical use for treatment of type 2 diabetes (T2DM). Accumulating evidence suggests PPARγ agonists may be useful for treating or delaying the onset of Alzheimer's dise ... Full text Link to item Cite

The cis-regulatory effect of an Alzheimer's disease-associated poly-T locus on expression of TOMM40 and apolipoprotein E genes.

Journal Article Alzheimers Dement · September 2014 BACKGROUND: We investigated the genomic region spanning the Translocase of the Outer Mitochondrial Membrane 40-kD (TOMM40) and Apolipoprotein E (APOE) genes, that has been associated with the risk and age of onset of late-onset Alzheimer's disease (LOAD) t ... Full text Link to item Cite

New applications of disease genetics and pharmacogenetics to drug development.

Journal Article Curr Opin Pharmacol · February 2014 TOMMORROW is a Phase III delay of onset clinical trial to determine whether low doses of pioglitazone, a molecule that induces mitochondrial doubling, delays the onset of MCI-AD in normal subjects treated with low dose compared to placebo. BOLD imaging stu ... Full text Link to item Cite

TOMM40 and APOE: Requirements for replication studies of association with age of disease onset and enrichment of a clinical trial.

Journal Article Alzheimers Dement · March 2013 A number of recent studies have not replicated the association of the translocase of the outer mitochondrial membrane pore subunit (TOMM40) rs10524523 polymorphism, which is in linkage disequilibrium with apolipoprotein E (APOE), with age of onset of Alzhe ... Full text Link to item Cite

Using genetics to enable studies on the prevention of Alzheimer's disease.

Journal Article Clin Pharmacol Ther · February 2013 Curing Alzheimer's disease (AD) remains an elusive goal; indeed, it may even prove to be impossible, given the nature of the disease. Although modulating disease progression is an attractive target and will alleviate the burden of the most severe stages, t ... Full text Link to item Cite

Clinical Trials of AD Delay of Onset: Enrichment by a Prognostic Genetic Biomarker

Book · January 1, 2013 Modern medicine is shifting its focus to predictive and preventive healthcare utilization. To support this change, early intervention clinical trials that delay the onset of symptomatic disease must be conducted in a safe and cost-effective manner, and wit ... Full text Cite

Characterization of the poly-T variant in the TOMM40 gene in diverse populations.

Journal Article PLoS One · 2012 We previously discovered that a polymorphic, deoxythymidine-homopolymer (poly-T, rs10524523) in intron 6 of the TOMM40 gene is associated with age-of-onset of Alzheimer's disease and with cognitive performance in elderly. Three allele groups were defined f ... Full text Link to item Cite

The importance of being connected.

Journal Article J Alzheimers Dis · 2011 Full text Link to item Cite

A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer's disease.

Journal Article Pharmacogenomics J · October 2010 The ɛ4 allele of the apolipoprotein E (APOE) gene is currently the strongest and most highly replicated genetic factor for risk and age of onset of late-onset Alzheimer's disease (LOAD). Using phylogenetic analysis, we have identified a polymorphic poly-T ... Full text Link to item Cite

Alzheimer's disease: diagnostics, prognostics and the road to prevention.

Journal Article EPMA J · June 2010 Alzheimer's disease (AD) presents one of the leading healthcare challenges of the 21st century, with a projected worldwide prevalence of >107 million cases by 2025. While biomarkers have been identified, which may correlate with disease progression or subt ... Full text Link to item Cite

Genetic variation at a single locus and age of onset for Alzheimer's disease.

Journal Article Alzheimers Dement · March 2010 This perspective article provides an opportunity to explain a new genetic finding for late-onset Alzheimer's disease (LOAD). It is specifically written for physicians and scientists who are interested in LOAD, but it may be relevant to those interested in ... Full text Link to item Cite

Pipeline pharmacogenetics: a novel approach to integrating pharmaco-genetics into drug development.

Journal Article Curr Pharm Des · 2009 There has been a decline in the number of new drugs registered over the past decade and regulatory concerns for safety as well as payer concerns for efficacy have focused attention on stratified medicine. Integration of pharmacogenetics into the drug devel ... Full text Link to item Cite

Traversing the cell cycle: The calcium/calmodulin connection.

Chapter · 1999 With twenty-seven chapters written by prominent scientists in cell research, this book is the first exhaustive attempt to cover the topic and fill a gap in the rapidly expanding area of calcium signaling. ... Cite

The mitotic peptidyl-prolyl isomerase, Pin1, interacts with Cdc25 and Plx1.

Journal Article EMBO J · August 10, 1998 The cis/trans peptidyl-prolyl isomerase, Pin1, is a regulator of mitosis that is well conserved from yeast to man. Here we demonstrate that depletion of Pin1-binding proteins from Xenopus egg extracts results in hyperphosphorylation and inactivation of the ... Full text Link to item Cite

Function of the hydrophilic carboxyl terminus of type II DNA topoisomerase from Drosophila melanogaster. I. In vitro studies.

Journal Article J Biol Chem · October 5, 1993 The function of the hydrophilic carboxyl-terminal region of Drosophila DNA topoisomerase II was examined by constructing a series of deletion mutants at the 3'-end of the Drosophila Top2 cDNA. The truncated enzymes were then expressed in Saccharomyces cere ... Link to item Cite

Function of the hydrophilic carboxyl terminus of type II DNA topoisomerase from Drosophila melanogaster. II. In vivo studies.

Journal Article J Biol Chem · October 5, 1993 Genetic complementation, protein distribution, and in vivo enzymatic activity by carboxyl-terminal truncation mutations of the Drosophila enzyme were examined. Removal of more than 273 of the 1447 amino acids composing the full-length topoisomerase inactiv ... Link to item Cite

STRUCTURES AND FUNCTIONS OF DNA TOPOISOMERASES

Conference JOURNAL OF CELLULAR BIOCHEMISTRY · February 8, 1993 Link to item Cite