Innovative blood platelets biomarker for early diagnosis of alzheimer's disease
First Claim
1. A method for determining an increased likelihood of Alzheimer'"'"'s disease in a patient, said method comprising the steps of:
- characterizing quantities of high and low molecular weight Tau protein variants in a reference population of persons not suffering from Alzheimer'"'"'s disease;
obtaining and stabilizing platelets from a patient;
extracting Tau protein variants from said platelets;
using said extracted Tau protein variants, analyzing platelet proteins electrophoresis pattern in 1-D and 2-D gels;
performing immunoassay with Tau5 anti-Tau antibodies directed against total Tau and using at least one antibody directed against hyperphosphorylated Tau selected from the group consisting of AT8 and PHF1 anti-Tau antibodies, thereby identifying Tau protein variants;
comparing the relative amounts of high and low molecular weight Tau protein variants in the platelets of said patient to that of said reference population and determining an increased likelihood of Alzheimer'"'"'s disease in a patient when the ratio of high to low molecular weight Tau protein variants in the immunoassay results exceeds said ratio in the reference population;
wherein low molecular weight Tau protein variants are those of weight less than 70 kDa and high molecular weight Tau protein variants are those of weight greater than 70 kDa.
3 Assignments
0 Petitions
Accused Products
Abstract
The present invention is directed to a method for early, non-invasive, rapid, efficient, reliable and accurate diagnose of Alzheimer'"'"'s disease. The present invention particularly addresses obtaining blood samples, and stabilizing platelets from healthy persons and patients with probable cognitive impairment and/or Alzheimer'"'"'s disease; extracting proteins from the platelets; identifying both monomeric and oligomeric tau proteins in the platelets with at least two monoclonal antibodies against the tau proteins, quantifying the amounts of the identified tau proteins, and comparing the amounts and protein profiles of the tau molecular species in the platelets of the healthy person and the patient.
5 Citations
12 Claims
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1. A method for determining an increased likelihood of Alzheimer'"'"'s disease in a patient, said method comprising the steps of:
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characterizing quantities of high and low molecular weight Tau protein variants in a reference population of persons not suffering from Alzheimer'"'"'s disease; obtaining and stabilizing platelets from a patient; extracting Tau protein variants from said platelets; using said extracted Tau protein variants, analyzing platelet proteins electrophoresis pattern in 1-D and 2-D gels; performing immunoassay with Tau5 anti-Tau antibodies directed against total Tau and using at least one antibody directed against hyperphosphorylated Tau selected from the group consisting of AT8 and PHF1 anti-Tau antibodies, thereby identifying Tau protein variants; comparing the relative amounts of high and low molecular weight Tau protein variants in the platelets of said patient to that of said reference population and determining an increased likelihood of Alzheimer'"'"'s disease in a patient when the ratio of high to low molecular weight Tau protein variants in the immunoassay results exceeds said ratio in the reference population; wherein low molecular weight Tau protein variants are those of weight less than 70 kDa and high molecular weight Tau protein variants are those of weight greater than 70 kDa. - View Dependent Claims (2, 3, 4)
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5. A method for determining a likelihood of Alzheimer'"'"'s disease in a patient, said method comprising the steps of:
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obtaining and stabilizing platelets from a patient; extracting Tau protein variants from said platelets; analyzing platelet proteins electrophoresis pattern in 1-D and 2-D gels and immunoassay; using antibodies, identifying Tau protein variants in platelets which h include at least two monoclonal antibodies directed against Tau, where at least one of them is directed against hyperphosphorylated variants of Tau protein, and characterizing these variants as low or high molecular weight Tau protein variants; and determining a likelihood of Alzheimer'"'"'s disease in said patient when the ratio of high to low molecular weight Tau protein variants exceeds 1; wherein low molecular weight Tau protein variants are those of 70 kDa or less, high molecular weight Tau protein variants are those greater than 70 kDa, and said antibodies are Tau5 anti-Tau antibodies and at least one from the group consisting of AT8 and PHF1 anti-Tau antibodies. - View Dependent Claims (6, 7, 8)
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9. A method for determining an increased likelihood of Alzheimer'"'"'s disease in a patient, said method comprising the steps of:
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obtaining and stabilizing platelets from a patient; extracting Tau protein variants from said platelets; analyzing platelet proteins electrophoresis pattern in 1-D and 2-D gels and immunoassay thereby identifying Tau protein variants and determining their molecular weight; characterizing Tau protein variants in platelets which includes using at least two monoclonal antibodies to Tau;
where at least one monoclonal antibody is directed to hyperphosphorylated variants of Tau protein which are high molecular weight variants if greater than 70 kDa, and characterizing Tau protein variants with molecular weight at 70 kDa or below as low molecular weight variants;separately quantifying the amounts of the extracted Tau protein variants by high and low molecular weight by densitometry of Tau protein variants, wherein the low molecular weight variants are identified by immunoreactivity to Tau5 anti-Tau antibodies and the high molecular weight Tau protein variants are identified by immunoreactivity to at least one anti-Tau antibody selected from the group consisting of AT8 anti-Tau antibodies and PHF1 anti-Tau antibodies; and determining an increased likelihood of Alzheimer'"'"'s disease in a patient when the ratio of high to low molecular weight Tau protein variants exceeds 1. - View Dependent Claims (10, 11, 12)
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Specification