Test and model for Alzheimer's disease
AssigneeElan Pharmaceuticals, Inc.
InventorsJohn Anthony Hardy, Marie-Christine Chartier-Harlin, Alison Mary Goate, Michael John Owen, Michael John Mullan
Life of this patent
Estimating the term…
Abstract
Model systems of Alzheimer's disease comprise a DNA sequence encoding an amyloid precursor protein (APP) isoform or fragment that has an amino acid substitution. The substituted amino acid may be other than valine at the amino acid position corresponding to amino acid residue position 717 of APP770. Methods of determining genetic predisposition to Alzheimer's disease are also disclosed.
Claims39
An isolated polynucleotide comprising a nucleic acid sequence encoding a codon 717 mutant of human amyloid precursor protein 770 (APP770), or an isoform or fragment of APP770 having a mutant amino acid residue at the position encoded by codon 717.
A composition comprising a polynucleotide probe capable of specifically hybridizing to an amyloid precursor protein 770 (APP770) allele exhibiting a mutation at codon 717.
A transgenic host comprising a nucleic acid segment encoding a position 717 mutant of human amyloid precursor protein 770 (APP770), or an APP770 isoform or fragment of APP770 having the mutation.
A transgenic non-human animal with germ cells or somatic cells comprising a heterologous gene encoding a position 717 mutant amyloid precursor protein 770 (APP770), which gene upon expression promotes neuropathological characteristics of Alzheimer's disease in the animal.
A cultured human primary or immortalized cell, comprising a nucleic acid segment encoding a position 717 mutant of human amyloid precursor protein 770 (APP770), or an APP770 isoform or fragment of APP770 having the mutation.
A diagnostic method for determining an inherited predisposition to Alzheimer's disease in a subject, comprising detecting in the subject the presence of an allele of amyloid precursor protein (APP), an isoform or fragment thereof, wherein said allele has a sequence polymorphism at a position 5 corresponding to codon 717 of APP770.
A method for genetic analysis of a human subject which comprises detecting the presence or absence of at least one polymorphism at codon 717 of an APP770 gene of an amyloid precursor protein (APP) gene in the subject.
A composition comprising a polypeptide free from human proteins, comprising a core sequence:
- Ile-Ala-Thr-Val-Ile-X-Ile-Thr-Leu-[SEQ ID NO:6]
- wherein X is any of the twenty conventional amino acids except valine.
An isolated polynucleotide, comprising a nucleic acid sequence encoding a mutant human APP allele that cosegregates with a genetic predisposition to Alzheimer's disease.
A method of determining a genetic predisposition of a subject to Alzheimer's disease, the method comprising detecting in the subject's DNA the presence of an allele of a gene encoding amyloid precursor protein (APP).
Dependencies are inferred from the claim text.