Scholars@Duke
Warren James Strittmatter

Warren James Strittmatter

Professor Emeritus of Neurology
Neurology, Behavioral Neurology
warren@neuro.duke.edu
Duke Box 2900, Durham, NC 27710
227H Bryan Res Bldg, Durham, NC 27710

Overview

Apolipoprotein (apoE) has been recently implicated in the pathogenesis of Alzheimer's disease (A.D.). One of the apoE alleles, e4, behaves as an autosomal co-dominant trait in the majority of late-onset and sporadic A.D.. The aopE4 gene dose is a major risk-factor susceptibility gene for A.D. with homozygosity for this allele virtually sufficient to cause disease by age 80, and with 50% of homozygous patients developing disease by age 68. Incontrast, the e2 and e3 alleles decrease the probability of disease, and increase the age of onset. Thus the inherited apoE allele determines in part, the risk of developing A.D., and determines the rate of disease progression. Interactions of apoE protein with other molecules is therefore critical in the disease process, with isoforms-specific interactions of apoE determining th eprobability, and rate, of disease expression.
The three common protein isoforms of apoE; E2, E3, E4, differ from each other by one amino acid, which determines their profoundly differing interactions with other proteins. In vitro, apoE4 binds BA peptide faster, and with a different pH dependence, than does apoE3. This isoform-specific difference observed in vitro correlates with the greater BA peptide amyloid burden deposited in situ in homozygous e4 A.D. patients, compared with homozygous e3 A.D. patients. Paired-helical filaments of the neurofibrillary tangle are composed of tau protein. ApoE3 avidly binds tau in vitro, forming a complex not disociated by boiling in SDS. In contrast, apoE4 does not form such a complex. Isoform-specific interactions of apoE with tau could alter tau function or metabolism.

Current Appointments & Affiliations

Professor Emeritus of Neurology · 2014 - Present Neurology, Behavioral Neurology, Neurology

Recent Publications

Inhibition of protein misfolding/aggregation using polyglutamine binding peptide QBP1 as a therapy for the polyglutamine diseases.

Journal Article Neurotherapeutics · July 2013 Protein misfolding and aggregation in the brain have been recognized to be crucial in the pathogenesis of various neurodegenerative diseases, including Alzheimer's, Parkinson's, and the polyglutamine (polyQ) diseases, which are collectively called the "pro ... Full text Link to item Cite

Bathing the brain.

Journal Article J Clin Invest · March 2013 The brain and spinal cord are surrounded by cerebrospinal fluid, which provides a mechanically stable environment for these delicate structures against the forces of gravity and sudden acceleration and deceleration. Neurons and glia comprising the parenchy ... Full text Link to item Cite

Alzheimer’s disease: the new promise.

Journal Article J Clin Invest · April 2012 Clinical vignette: A 59-year-old aeronautical engineer is referred to you for evaluation because of increasing difficulty with job performance over the last several years. Difficulty managing home finances, getting lost driving, and forgetting appointments ... Full text Link to item Cite
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Recent Grants

Trangenic Mouse Model of Alzheimer's Disease

ResearchMentor · Awarded by National Institutes of Health · 2003 - 2006

Manipulation of polyglutamine-protein interactions

ResearchCollaborator · Awarded by National Institutes of Health · 2000 - 2003

Alzheimer'S Disease Research Center

ResearchCo-Principal Investigator · Awarded by National Institutes of Health · 1985 - 1999

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Education, Training & Certifications

Duke University · 1973 M.D.