Abstract: Methods are provided for measuring glio-vascular pathway (“glymphatic system”) function in the brain of a mammal which include performing imaging of the brain and measuring cerebrospinal fluid-interstitial fluid (CSF-ISF) exchange in the brain. The methods can be used to track the exchange between CSF and ISF compartments. An imaging agent is optionally administered intrathecally. The imaging agent can be a negative or positive (paramagnetic) contrast agent and dynamic or contrast-enhanced magnetic resonance imaging (MRI) of the brain can be performed. The imaging agent can be a positron-emitting radionuclide tracer and positron emission tomography (PET) can be performed. Methods for treating diseases or disorders of the mammalian brain are also provided, in which the methods increase or decrease glymphatic clearance.

Abstract: Methods are provided for measuring glio-vascular pathway (“glymphatic system”) function in the brain of a mammal which include performing imaging of the brain and measuring cerebrospinal fluid-interstitial fluid (CSF-ISF) exchange in the brain. The methods can be used to track the exchange between CSF and ISF compartments. An imaging agent is optionally administered intrathecally. The imaging agent can be a negative or positive (paramagnetic) contrast agent and dynamic or contrast-enhanced magnetic resonance imaging (MRI) of the brain can be performed. The imaging agent can be a positron-emitting radionuclide tracer and positron emission tomography (PET) can be performed. Methods for treating diseases or disorders of the mammalian brain are also provided, in which the methods increase or decrease glymphatic clearance.

Abstract: Small molecules are used to inhibit specific receptor-ligand interaction between Alzheimer's amyloid-? peptide (A?) and Receptor for Advanced Gly-cation Endproducts (RAGE). Objectives include treating Alzheimer's disease and other pathologies involving cerebral amyloid angiopathy; improving blood flow to or within the brain; decreasing the level of A? in the brain; reducing neuropathology associated with Alzheimer's disease; reducing inflammation and/or oxidant stress in the brain; improving memory and/or learning; treating other conditions involving A?/RAGE interaction at the blood-brain barrier, RAGE-mediated transport of A? into the brain, or RAGE activation in brain vasculature and/or brain parenchyma (e.g., diabetic complications); or any combination thereof.

Abstract: A mutant low-density lipoprotein receptor related protein-1 binds to Alzheimer amyloid-beta (A?) peptide with greater affinity compared to its wild-type homolog. This binding may be used to detect A? or to separate A? from the rest of a subject's body. In Alzheimer disease, it may be used to provide diagnostic results by detecting A?, treatment by removing A?, or both.

Abstract: Small molecules are used to inhibit specific receptor-ligand interaction between Alzheimer's amyloid-? peptide (A?) and Receptor for Advanced Gly-cation Endproducts (RAGE). Objectives include treating Alzheimer's disease and other pathologies involving cerebral amyloid angiopathy; improving blood flow to or within the brain; decreasing the level of A? in the brain; reducing neuropathology associated with Alzheimer's disease; reducing inflammation and/or oxidant stress in the brain; improving memory and/or learning; treating other conditions involving A?/RAGE interaction at the blood-brain barrier, RAGE-mediated transport of A? into the brain, or RAGE activation in brain vasculature and/or brain parenchyma (e.g., diabetic complications); or any combination thereof.

Abstract: A soluble derivative of low-density lipoprotein receptor related protein-1 (sLRP-1) binds directly to Alzheimer's amyloid-? peptide (A?). This binding may be used to detect A? or to separate A? from the rest of a subject's body. In Alzheimer's disease, it may be used to provide diagnostic results by detecting A?, treatment by removing A?, or both.

Abstract: A soluble derivative of low-density lipoprotein receptor related protein-1 (sLRP-1) binds directly to Alzheimer's amyloid-? peptide (A?). This binding may be used to detect A? or to separate A? from the rest of a subject's body. In Alzheimer's disease, it may be used to provide diagnostic results by detecting A?, treatment by removing A?, or both.

Abstract: Neurovascular disorder critically contributes to the development and pathogenesis of Alzheimer's disease (AD). Transcriptional profiling of human brain endothelial cells (BEC) defines a subset of age-independent genes significantly altered in AD including the homebox gene GAX whose expression controls vascular phenotype and is low in AD. By using viral-mediated GAX gene silencing and transfer, restoring GAX expression in AD BEC is angio-genic, transcriptionally suppresses the AFX1 forkhead transcription factor-mediated apoptosis, and increases the levels of a major amyloid ?-peptide (A?) clearance receptor, the low density lipoprotein receptor-related protein 1 (LRP-1) at the blood-brain barrier. In a mouse model of Alzheimer's disease, deletion of the Gax gene results in reductions in brain capillary density and the resting cerebral blood flow, loss of angiogenic brain response to hypoxia, and an impaired A? brain efflux caused by reduced LRP-1 levels.

Abstract: Low-density lipoprotein receptor-related protein 2 (LRP2) is a potential receptor to regulate the level of apolipoprotein J (apoJ) in the central nervous system, which is the major carrier of amyloid-? peptide (A?). ApoJ is cleared from brain interstitial fluid (ISF) and cerebrospinal fluid (CSF) by LRP2-mediated transcytosis across epithelial and endothelial barriers. At physiological ISF/CSF levels, apoJ is rapidly transported by LRP2 across the blood-brain barrier (BBB). Importantly, apoJ also substantially enhances clearance from the brain of amyloidogenic A? isoforms (i.e., higher ?-sheet content such as A?42) as apoJ-A? by LRP2-mediated transport.

Abstract: A soluble derivative of low-density lipoprotein receptor related protein-1 (sLRP-1) binds directly to Alzheimer's amyloid-? peptide (A?). This binding may be used to detect A? or to separate A? from the rest of a subject's body. In Alzheimer's disease, it may be used to provide diagnostic results by detecting A?, treatment by removing A?, or both.