Abstract: Negatively charged nanoparticulate compositions are used to deliver therapeutic, prophylactic or diagnostic agents to macrophages or other phagocytic cells in the brain and central nervous system. The negative charge of the nanoparticles increases circulation, increases internalization by macrophage or other phagocytic cells, increases release within the macrophage or other phagocytic cells, or a combination thereof, relative to charge-neutral or charge-positive nanoparticles.

Abstract: Described herein are compositions and methods for enhancing peripheral macrophage A? phagocytosis activity. The methods include inhibiting the TGF-? signaling pathway and activating the BMP signaling pathway in peripheral macrophages to promote central nervous system infiltration and enhance macrophage A? phagocytosis activity. Inhibition of TGF-? signaling and activation of BMP signaling in peripheral macrophages represents an advantageous anti-amyloid therapeutic approach for Alzheimer's disease.

Abstract: The invention includes compositions and methods for enhancing peripheral macrophage A? phagocytosis activity. The invention includes inhibiting a component of TGF-? signaling pathway in peripheral macrophages to promote central nervous system infiltration and beneficial cerebral A? clearance. Inhibition of TGF-? signaling in peripheral macrophages represents an advantageous anti-amyloid therapeutic approach for Alzheimer's disease.

Abstract: There is provided a method of modifying vasoactivity by regulating a soluble A? pro-inflammatory pathway. Also provided is a method of modifying inflammatory reactions in microglia and neurons by regulating a soluble A? pro-inflammatory pathway. A method of treating patients with vascular disease by modifying an intracellular soluble A? pro-inflammatory pathway is also provided. A pharmaceutical composition consisting essentially of an effective amount of a soluble A? pro-inflammatory pathway regulator in a pharmaceutically effective carrier is also provided.

Abstract: There is provided a method of modifying vasoactivity by regulating a soluble A? pro-inflammatory pathway. Also provided is a method of modifying inflammatory reactions in microglia and neurons by regulating a soluble A? pro-inflammatory pathway. A method of treating patients with vascular disease by modifying an intracellular soluble A? pro-inflammatory pathway is also provided. A pharmaceutical composition consisting essentially of an effective amount of a soluble A? pro-inflammatory pathway regulator in a pharmaceutically effective carrier is also provided.

Abstract: Methods for assessing the risk of developing Alzheimer's Disease (AD), for diagnosing AD, and for measuring the progression of AD in a patient by determining CD45 isoform expression of blood cells obtained from the patient. The methods of the invention include determining CD45 isoform expression by cytometric analysis, quantitative Western immunoblotting, or quantitative RT-PCR or combinations thereof.

Abstract: The present invention provides a research model for screening compounds suspected of modulating the CD40L/CD40R signaling pathway by interfering with the CD40L/CD40R signaling pathway in an animal or human. Additionally, methods are provided for causing a desired biological effect in an individual or system afflicted with neuronal inflammation, brain injury/trauma, a tauopathy, or an amyloidogenic disease, as well as for the identification of compounds and/or small molecules capable of disrupting the CD40L/CD40R signaling pathway.

Abstract: Methods for screening compounds for use in the treatment of neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis, prion diseases, Huntington's disease, and Creutzfeldt-Jakob disease, where the screening methods include (a) measuring the vasoactivity of blood vessels when contacted sequentially with a &bgr;-amyloid peptide, phenylephrine, and a compound to be screened, and (b) measuring the inflammatory response, including cytokine release, when microglial cells are contacted with a &bgr;-amyloid peptide and then with a compound to be screened. The disclosed methods rely upon a common underlying mechanism for &bgr;-amyloid peptide-induced vasoactivity, &bgr;-amyloid peptide-induced inflammatory responses of microglial cells, and the pathogenesis of neurodegenerative diseases in general and Alzheimer's disease in particular, in which cGMP levels are increased by agents that counteract these three processes.

Abstract: The subject invention provides methods of treating amyloidogenic diseases, comprising the administration of therapeutically effective amounts of a composition comprising a carrier and an agent that interferes with the interaction of CD40L and CD40R to an individual afflicted with an amyloidogenic disease. Also provided are methods and/or assay systems for the identification of compounds or other small molecules capable of disrupting the CD40R/CD40L signaling pathway.