MEDI1814 selectively reduces free Aβ42 in cerebrospinal fluid of non-clinical species and Alzheimer's disease patients.

Introduction: Small molecules and antibodies are being developed to lower amyloid beta (Aβ) peptides.

Methods: We describe MEDI1814, a fully human high-affinity monoclonal antibody selective for Aβ, the pathogenic self-aggregating species of Aβ.

Results: MEDI1814 reduces free Aβ without impacting Aβ in the cerebrospinal fluid of rats and cynomolgus monkeys after systemic administration.

Vascular endothelial growth factor-D plasma levels and VEGFD genetic variants are independently associated with outcomes in patients with cardiovascular disease.

Aims: The vascular endothelial growth factor (VEGF) family is involved in pathophysiological mechanisms underlying cardiovascular (CV) diseases. The aim of this study was to investigate the associations between circulating VEGF ligands and/or soluble receptors and CV outcome in patients with acute coronary syndrome (ACS) and chronic coronary syndrome (CCS).

Methods And Results: Levels of VEGF biomarkers, including bFGF, Flt-1, KDR (VEGFR2), PlGF, Tie-2, VEGF-A, VEGF-C, and VEGF-D, were measured in the PLATO ACS cohort (n = 2091, discovery cohort).

Preclinical development of a high affinity α-synuclein antibody, MEDI1341, that can enter the brain, sequester extracellular α-synuclein and attenuate α-synuclein spreading in vivo.

There are no approved drug therapies that can prevent or slow the progression of Parkinson's disease (PD). Accumulation and aggregation of α-synuclein protein is observed throughout the nervous system in PD. α-Synuclein is a core component of Lewy bodies and neurites that neuropathologically define PD, suggesting that α-synuclein may be a key causative agent in PD.

Differential Effect of APOE Alleles on Brain Glucose Metabolism in Targeted Replacement Mice: An [F]FDG-μPET Study.

Background: The Apolipoprotein E (ApoE) alleles 2, 3, and 4 are known to differentially modulate cerebral glucose metabolism and the risk for Alzheimer's disease (AD) via both amyloid-β (Aβ)-dependent and independent mechanisms.

Objective: We investigated the influence of ApoE on cerebral glucose metabolism in humanized APOE Targeted Replacement (TR) mice at ages that precede the comparison of Aβ parenchymal deposits in APOE4-TR mice.

Methods: Fludeoxyglucose ([F]FDG) positron emission tomography (PET) measures were performed longitudinally in homozygous APOE-TR mice (APOE2, APOE3, APOE4;  = 10 for each group) at 3, 5, 11, and 15 months.