Abstract: A highly sensitive immunoassay has been developed and validated. In various embodiments, the assay comprises an immunoassay usable to measure soluble PDGFR? (sPDGFR-?) in a human biofluid sample such as cerebrospinal fluid (CSF). In various embodiments, elevated sPDGFR-? in a human biofluid sample reflects pericyte and blood-brain barrier (BBB) injury, and is therefore an early biomarker of human cognitive dysfunction, dementia, and/or Alzheimer's disease.

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: Protein S is a significant neuroprotectant when administered after focal ischemic stroke and prevents hypoxic/re-oxygenation injury. Purified human plasma-derived or recombinant protein S improves motor neurological function after stroke, and reduced brain infarction and edema. Protein S also enhances post-ischemic reperfusion and reduced brain fibrin and neutrophil deposition. Cortical neurons are protected from hypoxia/re-oxygenation-induced apoptosis. Thus, protein S and variants thereof are prototypes of a class of agents for preventing injury of the nervous system. In particular, a disease or other pathological condition (e.g., stroke) may be treated with such agents having one or more protein S activities (e.g., anti-thrombotic and anti-inflammatory activities, direct cellular neuronal protective effects) although the latter activities are not be required.

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: Brain endothelial low-density lipoprotein receptor related protein-1 (LRP-1) mediates vascular clearance of Alzheimer's amyloid-? peptide (A?) from the brain. Transport of A? occurs across the blood-brain barrier (BBB) to the systemic circulation, but the brain endothelium is compromised in Alzheimer's disease. The invention is used to diagnose the disease in symptomatic and asymptomatic individuals, to identify those at risk for disease or already affected thereby, to determine the stage of disease or its progression, to intervene earlier in or alter the disease's natural history, to provide a target for therapeutic or prophylactic treatments, to screen drugs or compare medical regimens, to determine the effectiveness of a drug or medical regimen, 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: Cerebral amyloid angiopathy is involved in Alzheimer dementia through reduction in arterial blood flow that may impair protein synthesis, which is required for learning and memory, and lower the threshold for ischemic injury. Elevated serum response factor (SRF) or myocardin (MYOCD) activity in subjects afflicted by or at risk for development of Alzheimer's disease (AD) promotes a “vascular smooth muscle cell” (VSMC) hypercontractile phenotype in brain arteries and enhance accumulation of A? in the vessel wall. This, in turn, can initiate a disease process in cerebral arteries which can cause brain arterial hypoperfusion and neurovascular uncoupling, that are commonly seen in AD. Thus, SRF and MYOCD represent novel targets for treating arterial dysfunction associated with cognitive decline in AD.

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: Activated protein C (APC), a prodrug, and/or a variant of APC may be used to inhibit undesirable effects of plasminogen activator: e.g., apoptosis or cell death of neurons and endothelial cells, brain hemorrhage or intracerebral bleeding, and/or tissue damage in a subject's brain. Inhibition appears to act through the extrinsic pathway of death receptor signal transduction. This represents an improvement in treatment using plasminogen activator (e.g., fibrinolysis). By reducing undesirable effects, the window for fibrinolytic therapy by plasminogen activator may be widened.

Abstract: Brain endothelial low-density lipoprotein receptor related protein-1 (LRP-1) mediates vascular clearance of Alzheimer's amyloid-&bgr; peptide (A&bgr;) from the brain. Transport of A&bgr; occurs across the blood-brain barrier (BBB) to the systemic circulation, but the brain endothelium is compromised in Alzheimer's disease. The invention is used to diagnose the disease in symptomatic and asymptomatic individuals, to identify those at risk for disease or already affected thereby, to determine the stage of disease or its progression, to intervene earlier in or alter the disease's natural history, to provide a target for therapeutic or prophylactic treatments, to screen drugs or compare medical regimens, to determine the effectiveness of a drug or medical regimen, or any combination thereof.

Abstract: Changes in the gene expression profile of vascular endothelium are associated with or may be a cause for Alzheimer's disease. This observation can be used to diagnose the disease in symptomatic or asymptomatic individuals, to identify those at risk for disease or already affected thereby, to determine the stage of disease or the disease's progression, to intervene earlier in or alter the natural history of the disease, to provide targets for therapeutic or prophylactic treatments, to screen drugs or otherwise compare medical regimens, to determine the effectiveness of a drug or medical regimen, or any combination thereof. Gene expression may be profiled at the level of transcription (e.g., products like hnRNA, mRNA, and other RNA) and/or translation (e.g., products like nascent polypeptide, mature protein, and other processed or modified proteins).