Abstract: Orthogonal IL-21 receptors and orthogonal IL-21 cytokines are described. The IL-21 receptor-cytokine pairs may include an orthogonal interleukin-21 receptor ? chain (“ortho-IL-21R?”) that has impaired binding to native interleukin-21 cytokine (“IL-21”) and an orthogonal IL-21 cytokine (“ortho-IL-21”) that has impaired binding to native IL-21R?, wherein the ortho-IL-21R? binds to the ortho-IL-21. The IL-21 receptor-cytokine pair may activate IL-21 signaling. Cells engineered to express the orthogonal IL-21 receptors are also described, as well as methods for using such cells for treatment of various diseases and disorders.

Abstract: Methods and kits are provided for amplifying and detecting misfolded tau protein from samples, for example, from patients having tauopathies such as Alzheimer's Disease, Progressive Supranuclear Palsy, and the like.

Abstract: Methods and kits are provided for amplifying and detecting misfolded tau protein from samples, for example, from patients having tauopathies such as Alzheimer's Disease, Progressive Supranuclear Palsy, and the like.

Abstract: Methods and kits are provided for amplifying and detecting ?S proteins from samples, for example, from patients having Parkinson's Disease. For example, a method for determining a presence of a soluble, misfolded ?S protein may include: contacting the sample with a monomeric, folded ?S protein to form an incubation mixture; conducting an incubation cycle two or more times on the incubation mixture effective to form an amplified portion of misfolded ?S protein; incubating the incubation mixture effective to cause misfolding and/or aggregation of at least a portion of the monomeric, folded ?S protein in the presence of the soluble, misfolded ?S protein; physically disrupting the incubation mixture effective to at least partly de-aggregate at least a portion of a misfolded ?S aggregate present; and determining the presence of the soluble, misfolded ?S protein in the sample by detecting at least a portion of the soluble, misfolded ?S protein.

Abstract: Methods and kits are provided for amplifying and detecting ?S proteins from samples, for example, from patients having Parkinson's Disease. For example, a method for determining a presence of a soluble, misfolded ?S protein may include: contacting the sample with a monomeric, folded ?S protein to form an incubation mixture; conducting an incubation cycle two or more times on the incubation mixture effective to form an amplified portion of misfolded ?S protein; incubating the incubation mixture effective to cause misfolding and/or aggregation of at least a portion of the monomeric, folded ?S protein in the presence of the soluble, misfolded ?S protein; physically disrupting the incubation mixture effective to at least partly de-aggregate at least a portion of a misfolded ?S aggregate present; and determining the presence of the soluble, misfolded ?S protein in the sample by detecting at least a portion of the soluble, misfolded ?S protein.

Abstract: Methods and kits are provided for amplifying and detecting misfolded proteins from samples, for example, from patients having Alzheimer's Disease, Parkinson's Disease, and the like. For example, a method for determining a presence of soluble, misfolded protein in a sample may include contacting the sample with a monomeric, folded protein to form an incubation mixture; conducting an incubation cycle two or more times effective to form an amplified portion of misfolded protein; incubating the incubation mixture effective to cause misfolding and/or aggregation of at least a portion of the monomeric, folded protein; physically disrupting the incubation mixture effective to break up at least a portion of any protein aggregate present; and determining the presence of the soluble, misfolded protein in the sample by detecting at least a portion of the soluble, misfolded protein. The monomeric, folded protein and the soluble, misfolded protein may exclude prion protein (PrP) and isoforms thereof.

Abstract: Methods and kits for evaluating a subject for a brain injury are described. The method may include providing at least one biological sample from the subject having or suspected of having the brain injury. The method may include conducting one or more amplification reactions, including contacting a portion of the biological sample with a monomeric, folded tau protein to form an incubation mixture. Each amplification reaction may include determining a presence or amount of the misfolded tau protein in the biological sample according to the amplified portion of the misfolded tau protein. Methods for evaluating the risk of neurodegenerative disease or disorder in a subject having suffered from brain injury are also described.

Abstract: Methods and kits are provided for amplifying and detecting misfolded tau protein from samples, for example, from patients having tauopathies such as Alzheimer's Disease, Progressive Supranuclear Palsy, and the like.

Abstract: Methods and kits are provided for amplifying and detecting A? proteins from samples, for example, from patients having Alzheimer's Disease. For example, a method for determining a presence of a soluble, misfolded A? protein may include contacting the sample with a monomeric, folded A? protein to form an incubation mixture; conducting an incubation cycle two or more times on the incubation mixture effective to form an amplified portion of misfolded A? protein; incubating the incubation mixture effective to cause misfolding and/or aggregation of at least a portion of the monomeric, folded A? protein; physically disrupting the incubation mixture effective to at least partly de-aggregate at least a portion of a misfolded A? aggregate present; and determining the presence of the soluble, misfolded A? protein in the sample by detecting at least a portion of the amplified portion of misfolded A? protein.

Abstract: Methods and kits are provided for amplifying and detecting misfolded proteins from samples, for example, from patients having Alzheimer's Disease, Parkinson's Disease, and the like. For example, a method for determining a presence of soluble, misfolded protein in a sample may include contacting the sample with a monomeric, folded protein to form an incubation mixture; conducting an incubation cycle two or more times effective to form an amplified portion of misfolded protein; incubating the incubation mixture effective to cause misfolding and/or aggregation of at least a portion of the monomeric, folded protein; physically disrupting the incubation mixture effective to break up at least a portion of any protein aggregate present; and determining the presence of the soluble, misfolded protein in the sample by detecting at least a portion of the soluble, misfolded protein. The monomeric, folded protein and the soluble, misfolded protein may exclude prion protein (PrP) and isoforms thereof.

Abstract: Methods and kits are provided for amplifying and detecting A? proteins from samples, for example, from patients having Alzheimer's Disease. For example, a method for determining a presence of a soluble, misfolded A? protein may include contacting the sample with a monomeric, folded A? protein to form an incubation mixture; conducting an incubation cycle two or more times on the incubation mixture effective to form an amplified portion of misfolded A? protein; incubating the incubation mixture effective to cause misfolding and/or aggregation of at least a portion of the monomeric, folded A? protein; physically disrupting the incubation mixture effective to at least partly de-aggregate at least a portion of a misfolded A? aggregate present; and determining the presence of the soluble, misfolded A? protein in the sample by detecting at least a portion of the amplified portion of misfolded A? protein.

Abstract: Methods and kits are provided for amplifying and detecting misfolded proteins from samples, for example, from patients having Alzheimer's Disease, Parkinson's Disease, and the like. For example, a method for determining a presence of soluble, misfolded protein in a sample may include contacting the sample with a monomeric, folded protein to form an incubation mixture; conducting an incubation cycle two or more times effective to form an amplified portion of misfolded protein; incubating the incubation mixture effective to cause misfolding and/or aggregation of at least a portion of the monomeric, folded protein; physically disrupting the incubation mixture effective to break up at least a portion of any protein aggregate present; and determining the presence of the soluble, misfolded protein in the sample by detecting at least a portion of the soluble, misfolded protein. The monomeric, folded protein and the soluble, misfolded protein may exclude prion protein (PrP) and isoforms thereof.

Abstract: Methods and kits are provided for amplifying and detecting A? proteins from samples, for example, from patients having Alzheimer's Disease. For example, a method for determining a presence of a soluble, misfolded A? protein may include contacting the sample with a monomeric, folded A? protein to form an incubation mixture; conducting an incubation cycle two or more times on the incubation mixture effective to form an amplified portion of misfolded A? protein; incubating the incubation mixture effective to cause misfolding and/or aggregation of at least a portion of the monomeric, folded A? protein; physically disrupting the incubation mixture effective to at least partly de-aggregate at least a portion of a misfolded A? aggregate present; and determining the presence of the soluble, misfolded A? protein in the sample by detecting at least a portion of the amplified portion of misfolded A? protein.

Abstract: Methods and kits are provided for amplifying and detecting ?S proteins from samples, for example, from patients having Parkinson's Disease. For example, a method for determining a presence of a soluble, misfolded ?S protein may include: contacting the sample with a monomeric, folded ?S protein to form an incubation mixture; conducting an incubation cycle two or more times on the incubation mixture effective to form an amplified portion of misfolded ?S protein; incubating the incubation mixture effective to cause misfolding and/or aggregation of at least a portion of the monomeric, folded ?S protein in the presence of the soluble, misfolded ?S protein; physically disrupting the incubation mixture effective to at least partly de-aggregate at least a portion of a misfolded ?S aggregate present; and determining the presence of the soluble, misfolded ?S protein in the sample by detecting at least a portion of the soluble, misfolded ?S protein.