4D flow MRI of CSF dynamics: relations to CSF morphology and Aβ status.

Background: Cerebrospinal fluid (CSF) dynamics are increasingly studied to understand potential pathologic coupling with neurological disorders. In Alzheimer’s disease (AD), CSF dynamics may be altered secondary to AD‐related atrophy and enlarged CSF spaces. Additionally, animal studies suggest that altered CSF dynamics could impair clearance of metabolic waste, leading to accumulation of amyloid‐beta (Aβ).

White matter hyperintensity onset, trajectories, and associations with cognitive decline in the presence of amyloid and tau.

Background: Cognitive decline is often influenced by Alzheimer’s disease (AD) pathology (e.g., beta‐amyloid burden) and other pathology (e.

4D flow MRI of CSF dynamics: relations to CSF morphology and Aβ status.

Background: Cerebrospinal fluid (CSF) dynamics are increasingly studied to understand potential pathologic coupling with neurological disorders. In Alzheimer’s disease (AD), CSF dynamics may be altered secondary to AD‐related atrophy and enlarged CSF spaces. Additionally, animal studies suggest that altered CSF dynamics could impair clearance of metabolic waste, leading to accumulation of amyloid‐beta (Aß).

A high-throughput chemotaxis assay for pharmacological characterization of chemokine receptors: Utilization of U937 monocytic cells.

Introduction: Higher-throughput chemotaxis assays have had limited use in chemokine receptor pharmacology studies mainly because of the unavailability of optimal assay formats in addition to an incompatibility of chemotactic cell backgrounds with other pharmacological assays. Here, we developed a high-throughput 96-well chemotaxis assay for leukocytic cell lines and identified the human U937 monocytic line as an excellent cell background for both chemotaxis and the high-throughput calcium mobilization Fluorescent Imaging Plate Reader (FLIPR) assay.

Methods: Optimal chemotactic conditions were developed using the Neuroprobe MBA96 nondisposable and the Millipore MultiScreen-MIC disposable apparatuses with responses to CXC chemokine receptor (CXCR)-4 endogenously expressed on the human H9 T lymphoma line, and confirmed with Jurkat T cell and U937 monocytic cell lines.

Pharmacological characterization of CXC chemokine receptor 3 ligands and a small molecule antagonist.

The CXC chemokine receptor 3 (CXCR3) is predominantly expressed on T helper type 1 (Th1) cells that are involved in inflammatory diseases. The three CXCR3 ligands CXCL9, CXCL10, and CXCL11 are produced at sites of inflammation and elicit migration of pathological Th1 cells. Here, we are the first to characterize the pharmacological potencies and specificity of a CXCR3 antagonist, N-1R-[3-(4-ethoxy-phenyl)-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl]-ethyl-N-pyridin-3-ylmethyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-acetamide (NBI-74330), from the T487 small molecule series.