Abstract: Enrichment of S and Z polymorphisms of alpha-1-antitrypsin (AAT) in distinct subsets of patients with cognitive disorder (pre-existing affective disorders and APOE2 allele carriers) suggests that AAT variants are potential endophenotypes for Alzheimer Disease and related disorders of cognition, behavior and affect. Such disorders include ADD/ADHD, learning disabilities, ADEM, and susceptibility to brain injury in toxic/chemical/biological/immunological events. In Alzheimer Disease, S and Z alleles affect age of onset and low AAT levels define faster progression rate. Twenty to thirty percent of all dementia patients display AAT and/or We polymorphisms. Effects of AAT may involve inflammation of liver/lung, macrophage activation and iron and lipid metabolism. AAT, its regulation, and iron metabolism represent therapeutic targets and AAT can serve as a biomarker for vulnerability and disease progression.

Abstract: A method of screening a subject for risk of developing Alzheimer's disease comprises determining the presence of at least one ApoE4 allele in a subject, and determining the presence or absence of decreased estrogen levels in said 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 said subject indicating said 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.

Abstract: 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.

Abstract: A method of screening a subject for risk of developing Alzheimer's disease comprises determining the presence of at least one ApoE4 allele in a subject, and determining the presence or absence of decreased estrogen levels in said 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 said subject indicating said 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.