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In another embodiment, the therapeutic molecule has at least one binding site specific for a target molecule that can be used to detect the presence of the target molecule (e.g., to detect a contaminant or diagnose a condition or disorder). In one embodiment, the therapeutic molecule modulates cellular activation or inhibition (e.g., by binding to a cell surface receptor and resulting in transmission of an activating or inhibitory signal). The invention further provides for a molecule according to the invention, for use for the treatment of one or more of the diseases associated with neuronal cells or referred to herein, such as a disease selected from Alzheimer's disease, progressive supranuclear palsy, Down syndrome, dementia pugilistica (chronic traumatic encephalopathy and other traumatic brain injury), frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), Lytico-Bodig disease (Parkinson-dementia complex of Guam), Tangle-predominant dementia, ganglioglioma, gangliocytoma, meningioangiomatosis, subacute sclerosing panencephalitis, lead encephalopathy, Hemimegalencephaly, tuberous sclerosis, Hallervorden-Spatz disease, Pick's disease, corticobasal ganglionic degeneration, argyrophilic grain disease, corticobasal degeneration, lipofuscinosis, frontotemporal dementia, supranuclear palsy, and frontotemporal lobar degeneration (reviewed in Frost et. In certain other embodiments, the disease or condition is a neurodegenerative disease with tauopathy, e.g., progressive supranuclear palsy, frontotemporal dementia-tau (FTD-tau), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), corticobasal degeneration (CBD), traumatic brain injury, chronic traumatic encephalopathy, HIV associated neurocognitive disorders, Argyrophilic grain disease, Down syndrome-Alzheimer's disease, Amnestic mild cognitive impairment-Alzheimer's disease, Parkinson's disease dementia, Hallervorden-Spatz disease (Pantothenate kinase-associated neurodegeneration), Niemann Pick disease type C, Myotonic dystrophy, Amyotrophic lateral sclerosis, Parkinson's disease or Huntington's disease.



In certain embodiments, the disease or condition is progressive supranuclear palsy, Down syndrome, dementia pugilistica (chronic traumatic encephalopathy and other traumatic brain injury), frontotempotal dementia with parkinsonism linked to chromosome 17 (FTDP-17), Lytico-Bodig disease (Parkinson-dementia complex of Guam), Tangle-predominant dementia, ganglioglioma, watch live sexcam gangliocytoma, meningioangiomatosis, subacute sclerosing panencephalitis, lead encephalopathy, Hemimegalencephaly, tuberous sclerosis, Hallervorden-Spatz disease, Pick's disease, corticobasal ganglionic degeneration, argyrophilic grain disease, corticobasal degeneration, lipofuscinosis, frontotemporal dementia, supranuclear palsy, and frontotemporal lobar degeneration, a disease of brain network dysfunction (e.g., all forms of epilepsy and depression), dravet syndrome, a spinal cord disorder, a peripheral neuropathy, a cranial nerve disorder (e.g., Trigeminal neuralgia), an autonomic nervous system disorder (e.g., dysautonomia or multiple system atrophy), a movement disorder of a central and peripheral nervous system (e.g., Parkinson's disease, essential tremor, amyotrophic lateral sclerosis, Tourette's Syndrome, multiple sclerosis or various types of peripheral neuropathy), a sleep disorder (e.g., Narcolepsy), migraine or other types of headache (e.g., cluster headache and tension headache), lower back and neck pain, central neuropathy, a neuropsychiatric illness, attention deficit hyperactivity disorder, autism, Huntington's disease, Rett Syndrome, Angelman syndrome, organic psychosis, an infection of the brain or spinal cord (including meningitis), or a prion disease), anemia, cancer, leukemia, an inflammatory condition or an autoimmune disease (e.g. arthritis, psoriasis, lupus erythematosus, multiple sclerosis), a bacterial infection, and any combination thereof.



Are you sitting down? For NOR, data are analyzed using either a paired t-test for within-group analyses or by an ANOVA followed by a Dunnett's post-hoc test for between group analyses. For Morris Water Maze (MWM), a repeated MWM ANOVA is used to analyze the acquisition phase and a one-way ANOVA followed by Dunnett's post-hoc for probe trial analyses. In some embodiments, statistical analyses for behavioral tests are conducted using GraphPad Prism (GraphPad Software, Inc., La Jolla, Calif.). Antigen binding portions can be produced by recombinant or biochemical methods that are well known in the art. In one embodiment, a molecule of the invention comprises at least one of a therapeutic molecule that is an antigen binding site (e.g., an antigen binding site of an antibody, antibody variant, or antibody fragment), a receptor binding portion of ligand, or a ligand binding portion of a receptor. In some embodiments, the molecules or conjugate of the invention is used in therapy. In still other embodiments, the method comprising a calcium oscillation assay, a sequence score method, and/or in vivo tolerability test can further comprise administering the selected molecule to a subject in need thereof.



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