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OwnerWolff M. Kirsch, Anto Lennart +4inventors
InventorsWolff M. Kirsch, Anto Lennart, Wayne J. Kelln, Dae-Kyung Kang, Rodney L. Levine, Tracey A. Rouault
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The present invention relates to the discovery of markers for neurodegenerative disease. More particularly, it was discovered that forms of IRP-2 protein that are unable to undergo oxidation at critical cysteine residues are diagnostic for neurodegenerative disease including, but not limited to Alzheimer's disease. Embodiments include nucleic acids that encode mutant IRP-2 proteins and fragments thereof, mutant IRP-2 proteins and fragments thereof, antibodies directed to epitopes present on mutant IRP-2 proteins and fragments thereof, methods of making these nucleic acids and polypeptides, as well as, approaches to diagnose neurodegenerative disease in animals, such as humans at risk of contracting Alzheimer's disease.
A purified or isolated nucleic acid comprising a sequence that encodes a peptide loop corresponding to amino acid residues 136-216 of wild-type IRP-2 from humans, wherein said sequence comprises a mutation in said peptide loop, wherein said mutation interferes with the ability of a cysteine residue present in said peptide loop to undergo oxidation.
A purified or isolated polypeptide comprising a peptide loop corresponding to amino acid residues 136-216 of wild-type IRP-2 from humans, wherein said sequence comprises a mutation in said peptide loop, wherein said mutation interferes with the ability of a cysteine residue present in said peptide loop to undergo oxidation.
A method of identifying a subject in need of treatment or prevention of a neurodegenerative disease comprising:
An antibody capable of specifically binding to a protein comprising an amino acid sequence selected from the group consisting of SEQ ID Nos. 4, 6, 8, 10, 12, 14, and 16.
A purified or isolated antibody capable of specifically binding a mutant IRP-2 protein but does not specifically bind wild-type IRP-2 protein, wherein said mutant IRP-2 protein comprises a mutation in a peptide loop that corresponds to the amino acid sequence of SEQ. ID. No. 2.
A method of differentiating mild cognitive impairment syndrome (MCI) from other forms of dementia in a human patient, comprising:
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