Abstract: A vaccine for delaying onset of or for treatment of Alzheimer's disease or an Alzheimer-related disorder in an individual comprises a therapeutically effective amount of a physiologically acceptable protofibril/oligomer comprising N-terminal truncated A?. An antibody for delaying an onset of or for treatment of Alzheimer's disease or an Alzheimer-related disorder in an individual hinds one or more truncated A? protofibrils/oligomers, but exhibits no or substantially no cross-reactivity with full length A? monomers, and optionally said antibody shows cross-reactivity to N-terminal truncated A? monomers. Methods for delaying an onset of or for treatment of Alzheimer's disease or an Alzheimer-related disorder employ the vaccine or antibody. Methods of detecting soluble N-terminal truncated amyloid-beta (A?) protofibrils/oligomers and N-terminal truncated A? monomers employ the antibody.

Abstract: The present invention relates to a brain delivery protein, comprising a target binding antibody which binds to a target in a mammalian brain; two carrier moieties, each of which being capable of monovalent interaction with a protein expressed on a blood brain barrier (BBB) endothelial cell, wherein each of said carrier moieties is linked to a C-terminal end of the target binding antibody. The present invention moreover relates to use of such brain delivery proteins in therapy or diagnosis or for research of e.g. neurodegenerative disorders, and other brain diseases.

Abstract: A method of preventing, alleviating or treating traumatic brain injury in an individual comprises administering to the individual a therapeutically effective and physiologically acceptable amount of an agent capable of reducing the amount of one or more aggregated forms of one or more peptides in the brain. An agent capable of reducing the amount of one or more aggregated forms of one or more peptides in the brain is suitable for use in preventing, alleviating or treating traumatic brain injury. A method for predication of the risk of an individual for complications after a traumatic brain injury comprises detecting one or more aggregated forms of one or more peptides prone to aggregate as a result of a traumatic brain injury event, in the brain of the individual, wherein an increased level of such aggregates in the brain indicates an increased risk for complications.

Abstract: Methods for detecting ?-synuclein oligomers in vivo comprise administering an antibody to an individual suspected of carrying soluble ?-synuclein, wherein the antibody is produced from a stabilized soluble ?-synuclein oligomer and is capable of binding the stabilized soluble ?-synuclein oligomer, wherein the stabilized soluble ?-synuclein oligomer has a lower formation rate to a non-soluble aggregated form than a non-stabilized soluble oligomer of the ?-synuclein, and wherein the antibody is labelled with a detectable marker; and detecting the presence of any complex formed between the antibody and soluble ?-synuclein by detection of the marker.

Abstract: The present invention relates to a brain delivery protein, comprising a target binding antibody which binds to a target in a mammalian brain; two carrier moieties, each of which being capable of monovalent interaction with a protein expressed on a blood brain barrier (BBB) endothelial cell, wherein each of said carrier moieties is linked to a C-terminal end of the target binding antibody. The present invention moreover relates to use of such brain delivery proteins in therapy or diagnosis or for research of e.g. neurodegenerative disorders, and other brain diseases.

Abstract: A method of preventing, alleviating or treating traumatic brain injury in an individual comprises administering to the individual a therapeutically effective and physiologically acceptable amount of an agent capable of reducing the amount of one or more aggregated forms of one or more peptides in the brain. An agent capable of reducing the amount of one or more aggregated forms of one or more peptides in the brain is suitable for use in preventing, alleviating or treating traumatic brain injury. A method for predication of the risk of an individual for complications after a traumatic brain injury comprises detecting one or more aggregated forms of one or more peptides prone to aggregate as a result of a traumatic brain injury event, in the brain of the individual, wherein an increased level of such aggregates in the brain indicates an increased risk for complications.

Abstract: Methods for detecting ?-synuclein oligomers in vivo comprise administering an antibody to an individual suspected of carrying soluble ?-synuclein, wherein the antibody is produced from a stabilized soluble ?-synuclein oligomer and is capable of binding the stabilized soluble ?-synuclein oligomer, wherein the stabilized soluble ?-synuclein oligomer has a lower formation rate to a non-soluble aggregated form than a non-stabilized soluble oligomer of the ?-synuclein, and wherein the antibody is labelled with a detectable marker; and detecting the presence of any complex formed between the antibody and soluble ?-synuclein by detection of the marker.

Abstract: Methods of treating or delaying onset of a neurodegenerative disorder with ?-synuclein pathology in an individual comprise administering an antibody which is produced from a stabilized soluble ?-synuclein oligomer and capable of binding a stabilized soluble ?-synuclein oligomer, the stabilized soluble ?-synuclein oligomer having a lower formation rate to a non-soluble aggregated form than a non-stabilized soluble oligomer of the ?-synuclein. The antibody has been collected from a non-human animal to which stabilized soluble ?-synuclein oligomer had been administered or has been produced by hybridoma technology, phage display, ribosome display, mammalian cell display or bacterial display, and the disorder with ?-synuclein pathology is characterized by deposition of Lewy bodies and Lewy neurites or is selected from the group consisting of Parkinson's disease (PD), dementia with Lewy bodies (DLB), the Lewy body variant of Alzheimer's disease, and multiple system atrophy (MSA).

Abstract: The invention relates to an isolated monoclonal antibody or antigen-binding fragment thereof that (a) binds (i) wild-type A? 42/40 protofibril comprising N-terminal truncated A? forms and (ii) A? 42/40 Arc protofibril comprising N-terminal truncated A? forms and (b) has no or little cross-reactivity to A? 42/40 monomers. The invention further relates to a method of using such an antibody to treat Alzheimer's disease.

Abstract: In an in vivo method for detecting ?-synuclein protofibrils in human tissue, an antibody or fragment thereof is administered to a human. The antibody or fragment is labelled with a detectable label. A complex formed between the antibody or fragment and ?-synuclein protofibrils in the human tissue is detected. The antibody or fragment has high affinity for human ?-synuclein protofibrils and low affinity for ?-synuclein monomers and has a combination of three specified variable heavy (VH) CDR sequences and three specified variable light (VL) CDR sequences.

Abstract: An in vivo method for detecting ?-synuclein protofibrils in human tissue comprises administering an antibody or fragment thereof to a human, wherein the antibody or fragment thereof is labelled with a detectable label, and detecting a complex formed between the antibody or fragment thereof and ?-synuclein protofibrils in the human tissue. The antibody or fragment thereof has high affinity for human ?-synuclein protofibrils and low binding of ?-synuclein monomers and has a combination of three specified variable heavy (VH) CDR sequences and three specified variable light (VL) CDR sequences.

Abstract: The invention relates to an isolated antibody, or fragment thereof, having high affinity for human A? protofibrils. The invention further relates to compositions that include the antibody, or a fragment thereof, and a pharmaceutically acceptable buffer. The invention further relates to a method of preventing or treating Alzheimer's disease, which includes the step of administering to a patient having or suspected of having Alzheimer's disease such an antibody, or fragment thereof or a composition that includes the antibody or a fragment thereof.

Abstract: The invention relates to an isolated monoclonal antibody or antigen-binding fragment thereof that (a) binds (i) wild-type A? 42/40 protofibril comprising N-terminal truncated A? forms and (ii) A? 42/40 Arc protofibril comprising N-terminal truncated A? forms and (b) has no or little cross-reactivity to A? 42/40 monomers. The invention further relates to a method of using such an antibody to treat Alzheimer's disease.

Abstract: Antibodies and fragments thereof have high affinity for human ?-synuclein protofibrils and low binding of ?-synuclein monomers, wherein the antibodies or fragments have specified Complementarity Determining Region (CDR) sequences. Compositions comprise such an antibody or fragment and methods of detecting ?-synuclein protofibrils use such an antibody or fragment. In further embodiments, methods of preventing, delaying onset of or treating a neurodegenerative disorder with ?-synuclein pathology comprise administering such an antibody or fragment, and such an antibody or fragment is used in the manufacture of a pharmaceutical composition for treatment of a neurodegenerative disorder with ?-synuclein pathology. Such an antibody or fragment is used in the diagnosis or monitoring of the development of a neurodegenerative disorder with ?-synuclein pathology, and in methods for reducing or inhibiting ?-synuclein aggregation by administration of such an antibody or fragment.

Abstract: Antibodies and fragments thereof have high affinity for human ?-synuclein protofibrils and low binding of ?-synuclein monomers, wherein the antibodies or fragments have specified Complementarity Determining Region (CDR) sequences. Compositions comprise such an antibody or fragment and methods of detecting ?-synuclein protofibrils use such an antibody or fragment. In further embodiments, methods of preventing, delaying onset of or treating a neurodegenerative disorder with ?-synuclein pathology comprise administering such an antibody or fragment, and such an antibody or fragment is used in the manufacture of a pharmaceutical composition for treatment of a neurodegenerative disorder with ?-synuclein pathology. Such an antibody or fragment is used in the diagnosis or monitoring of the development of a neurodegenerative disorder with ?-synuclein pathology, and in methods for reducing or inhibiting ?-synuclein aggregation by administration of such an antibody or fragment.

Abstract: Methods of treating or delaying onset of a neurodegenerative disorder with ?-synuclein pathology in an individual comprise administering an antibody which is produced from a stabilized soluble ?-synuclein oligomer and capable of binding a stabilized soluble ?-synuclein oligomer, the stabilized soluble ?-synuclein oligomer having a lower formation rate to a non-soluble aggregated form than a non-stabilized soluble oligomer of the ?-synuclein. The antibody has been collected from a non-human animal to which stabilized soluble ?-synuclein oligomer had been administered or has been produced by hybridoma technology, phage display, ribosome display, mammalian cell display or bacterial display, and the disorder with ?-synuclein pathology is characterized by deposition of Lewy bodies and Lewy neurites or is selected from the group consisting of Parkinson's disease (PD), dementia with Lewy bodies (DLB), the Lewy body variant of Alzheimer's disease, and multiple system atrophy (MSA).

Abstract: Antibodies and fragments thereof have high affinity for human ?-synuclein protofibrils and low binding of ?-synuclein monomers, wherein the antibodies or fragments have specified Complementarity Determining Region (CDR) sequences. Compositions comprise such an antibody or fragment and methods of detecting ?-synuclein protofibrils use such an antibody or fragment. In further embodiments, methods of preventing, delaying onset of or treating a neurodegenerative disorder with ?-synuclein pathology comprise administering such an antibody or fragment, and such an antibody or fragment is used in the manufacture of a pharmaceutical composition for treatment of a neurodegenerative disorder with ?-synuclein pathology. Such an antibody or fragment is used in the diagnosis or monitoring of the development of a neurodegenerative disorder with ?-synuclein pathology, and in methods for reducing or inhibiting ?-synuclein aggregation by administration of such an antibody or fragment.

Abstract: A vaccine for delaying an onset of or for treatment of an ?-synuclein-related disorder in an individual comprises a therapeutically effective amount of isolated stabilized soluble ?-synuclein oligomer having a lower formation rate to a non-soluble aggregated form than a non-stabilized oligomer of the ?-synuclein. An antibody for delaying an onset of or for treatment of an ?-synuclein-related disorder in an individual binds soluble ?-synuclein. Methods for delaying an onset of for treatment or for prevention of an ?-synuclein-related disorder employ the vaccine or antibody. Methods of detecting ?-synuclein oligomers employ the antibody.

Abstract: Antibodies and fragments thereof have high affinity for human ?-synuclein protofibrils and low binding of ?-synuclein monomers, wherein the antibodies or fragments have specified Complementarity Determining Region (CDR) sequences. Compositions comprise such an antibody or fragment and methods of detecting ?-synuclein protofibrils use such an antibody or fragment. In further embodiments, methods of preventing, delaying onset of or treating a neurodegenerative disorder with ?-synuclein pathology comprise administering such an antibody or fragment, and such an antibody or fragment is used in the manufacture of a pharmaceutical composition for treatment of a neurodegenerative disorder with ?-synuclein pathology. Such an antibody or fragment is used in the diagnosis or monitoring of the development of a neurodegenerative disorder with ?-synuclein pathology, and in methods for reducing or inhibiting ?-synuclein aggregation by administration of such an antibody or fragment.

Abstract: Antibodies and fragments thereof have high affinity for human ?-synuclein protofibrils and low binding of ?-synuclein monomers, wherein the antibodies or fragments have specified Complementarity Determining Region (CDR) sequences. Compositions comprise such an antibody or fragment and methods of detecting ?-synuclein protofibrils use such an antibody or fragment. In further embodiments, methods of preventing, delaying onset of or treating a neurodegenerative disorder with ?-synuclein pathology comprise administering such an antibody or fragment, and such an antibody or fragment is used in the manufacture of a pharmaceutical composition for treatment of a neurodegenerative disorder with ?-synuclein pathology. Such an antibody or fragment is used in the diagnosis or monitoring of the development of a neurodegenerative disorder with ?-synuclein pathology, and in methods for reducing or inhibiting ?-synuclein aggregation by administration of such an antibody or fragment.