Partnering with Big Pharma-What Academics Need to Know.

Knowledge of the parameters of drug development can greatly aid academic scientists hoping to partner with pharmaceutical companies. Here, we discuss the three major pillars of drug development-pharmacodynamics, pharmacokinetics, and toxicity studies-which, in addition to pre-clinical efficacy, are critical for partnering with Big Pharma to produce novel therapeutics.

Gantenerumab: a novel human anti-Aβ antibody demonstrates sustained cerebral amyloid-β binding and elicits cell-mediated removal of human amyloid-β.

The amyloid-β lowering capacity of anti-Aβ antibodies has been demonstrated in transgenic models of Alzheimer's disease (AD) and in AD patients. While the mechanism of immunotherapeutic amyloid-β removal is controversial, antibody-mediated sequestration of peripheral Aβ versus microglial phagocytic activity and disassembly of cerebral amyloid (or a combination thereof) has been proposed. For successful Aβ immunotherapy, we hypothesized that high affinity antibody binding to amyloid-β plaques and recruitment of brain effector cells is required for most efficient amyloid clearance.

Alzheimer's disease. Molecular consequences of presenilin-1 mutation.

Alzheimer's disease is characterized by accumulation in the brain of a family of insoluble amyloid peptides (Abeta peptides), which are produced as a result of the normal processing of beta-amyloid precursor protein (beta-APP). Russo et al. claim that a truncated Abeta peptide that lacks the first ten amino acids accumulates in the brains of patients carrying a mutant form of pre-senilin 1 (PS1), a protein that is involved in cleavage of beta-APP.

Genetics of Alzheimer's disease--routes to the pathophysiology.

Considerable advances have been made the last years in the understanding of the pathogenesis of Alzheimer's disease (AD): Several pathogenic mutations have been found in the amyloid precursor protein gene on chromosome 21. Two other dominantly operating genes on chromosome 14 and 1 were recently cloned, named presenilin 1 and 2, respectively. Mutations in these genes give rise to AD with a very early age of onset.

Quantification of Alzheimer amyloid beta peptides ending at residues 40 and 42 by novel ELISA systems.

Background: The amyloid beta (Abeta) peptide is a key molecule in the pathogenesis of Alzheimer's disease. Reliable methods to detect and quantify soluble forms of this peptide in human biological fluids and in model systems, such as cell cultures and transgenic animals, are of great importance for further understanding the disease mechanisms. In this study, the application of new and highly specific ELISA systems for quantification of Abeta40 and Abeta42 (Abeta peptides ending at residues 40 or 42, respectively) in human cerebrospinal fluid (CSF) are presented.