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US 11,906,530 B2Granted
Methods for the detection of tau protein aggregates
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsByron Winslow Caughey, Eri Saijo, Allison Lindsey Kraus, Michael Anthony Metrick, II
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Abstract
Methods are disclosed herein for determining whether a subject has a Tauopathy, such as Pick disease, Alzheimer disease, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) or argyrophilic grain disease (AGD). These methods utilize an amyloid seeding assay.
Claims35
A method of determining whether a subject has a 3R/4R Tauopathy, comprising:
- (a) performing a seeded Tau polymerization assay on a biological sample from the subject, comprising:
- (i) contacting the biological sample with a purified recombinant truncated Tau protein, wherein the recombinant truncated Tau protein consists of SEQ ID NO:
- 43 or SEQ ID NO:
- 44, to form a reaction mixture;
- (ii) incubating the reaction mixture to permit coaggregation of disease-associated Tau protein (TD) present in the biological sample with the recombinant truncated Tau protein;
- (iii) maintaining incubation conditions that promote coaggregation of the recombinant truncated Tau protein with the TD to result in a conversion of the recombinant truncated Tau protein to amyloid Tau protein aggregates while inhibiting development of spontaneously forming Tau protein aggregates (rT(spon));
- and
- (iv) agitating amyloid Tau protein aggregates formed during step (iii), wherein the agitating comprises shaking the reaction mixture in a shaking cycle, wherein each shaking cycle comprises a period of rest and a period of shaking;
- and
- (b) detecting amyloid Tau protein present in the reaction mixture, and wherein detection of amyloid Tau protein in the reaction mixture indicates that the subject has the 3R/4R Tauopathy.
7 more elements
A method of detecting 3R/4R Tau protein aggregates, comprising:
- (a) performing a seeded Tau polymerization assay on a biological sample from a subject, comprising:
- (i) contacting the biological sample with a purified recombinant truncated Tau protein, wherein the recombinant truncated Tau protein consists of SEQ ID NO:
- 43 or SEQ ID NO:
- 44, to form a reaction mixture;
- (ii) incubating the reaction mixture to permit coaggregation of 3R/4R disease-associated Tau protein (TD) present in the biological sample with the recombinant truncated Tau protein;
- (iii) maintaining incubation conditions that promote coaggregation of the recombinant truncated Tau protein with the TD to result in a conversion of the recombinant truncated Tau protein to amyloid Tau protein aggregates while inhibiting development of spontaneously forming Tau protein aggregates (rT(spon));
- and
- (iv) agitating amyloid Tau protein aggregates formed during step (iii), wherein the agitating comprises shaking the reaction mixture in a shaking cycle, wherein each shaking cycle comprises a period of rest and a period of shaking;
- and
- (b) detecting amyloid Tau protein present in the reaction mixture.
7 more elements
Dependencies are inferred from the claim text.