Duke University

Donald E Schmechel

Allen D Roses

Warren J Strittmatter

Jan J Enghild

Guy S Salvesen

Karl H Weisgraber

Michel Goedert

John R Gilbert

Laura W Shaughnessy

Ann M Saunders

Pu-Ting Xu

Gillian Einstein

A method of screening a subject for risk of developing Alzheimer's disease is carried out by determining the presence of at least one ApoE4 allele in a subject, and determining the presence or absence of decreased estrogen levels in the subject (e.g., due to previous or impending menopause or hysterectomy). The presence of at least one ApoE4 allele (and particularly two ApoE4 alleles) in combination with decreased estrogen levels in the subject indicating the subject is at greater risk of developing Alzheimer's disease (e.g., as compared to subjects with at corresponding number of ApoE4 alleles, but who do not have decreased estrogen levels), and that the subject will receive greater benefit from estrogen replacement therapy in treating Alzheimer's disease than a subject who does not carry one or two ApoE4 alleles.

Method of determining Alzheimer's disease risk using apolipoprotein E4 genotype analysis in combination with decreased estrogen levels

Methods of diagnosing or prognosing Alzheimer's disease in a subject are disclosed. The methods involve directly or indirectly detecting the presence or absence of an apolipoprotein E type 4 (ApoE4) isoform or DNA encoding ApoE4 in the subject. The presence of ApoE4 indicates the subject is afflicted with Alzheimer's disease or at risk of developing Alzheimer's disease. A novel immunochemical assay for detecting the presence or absence of the Apoliprotein E (ApoE) E4 allele in a subject is also disclosed.

Methods of detecting Alzheimer's disease

A method of combatting Alzheimer's disease which comprises increasing the binding of the tau protein in nerve cells of that subject, and/or the binding of MAP2c protein in nerve cells of that subject, to either Apolipoprotein E or an Apolipoprotein E fragments capable of binding tau and/or MAP2c. In one embodiment, the method comprises administering the ApoE or ApoE fragment to the subject; in another embodiment, the method comprises administering to the subject a vector capable of entering nerve cells, which vector then upregulates the expression of an ApoE or an ApoE fragment capable of binding tau and/or MAP2c in nerve cells. Compositions useful for carrying out these methods are also disclosed.

Methods and compositions for binding tau and MAP2c proteins

Apolipoprotein E isoform-specific monoclonal antibodies

A transgenic mouse that expresses the human Apo E isoforms Apo E2, Apo E3 or Apo E4 but is essentially incapable of expressing endogenous Apo E. Additionally, mice that express more than one of these isoforms are produced by selectively breeding the transgenic mice expressing the different Apo E isoforms disclosed herein. Thus, the present invention allows, among other things, the study of the effects of different combinations of human Apo E isoform expression on normal brain biology, development, function, aging and injury.

Creation of human apolipoprotein E isoform specific transgenic mice in

Methods of diagnosing or prognosing Alzheimer's disease in a subject are disclosed. The methods involve directly or indirectly detecting the presence or absence of an apolipoprotein E type 4 (ApoE4) isoform or DNA encoding ApoE4 in the subject. The presence of ApoE4 indicates the subject is at risk of developing Alzheimer's disease. A novel immunochemical assay for detecting the presence or absence of the Apoliprotein E (ApoE) E4 allele in a subject is also disclosed.

Kit for detecting the ApoE4 allele, and for diagnosing the existence or

Methods of diagnosing or prognosing Alzheimer's disease in a subject are disclosed. The methods involve directly or indirectly detecting the presence or absence of an apolipoprotein E type 4 (ApoE4) isoform or DNA, encoding ApoE4 in the subject. The presence of ApoE4 indicates the subject is afflicted with Alzheimer's disease or at risk of developing Alzheimer's disease. A novel immunochemical assay for detecting the presence or absence of the Apoliprotein E (ApoE) E4 allele in a subject is also disclosed.

Growing community of inventors

Durham, NC, United States of America

Donald E Schmechel