B Acad Nat Med Paris
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B Acad Nat Med Paris · Jun 2015
Strategy of translational research on Alzheimer's disease: targets, animal models and biomarkers.
Alzheimer's disease causes severe cognitive alterations in humans and is associated with two main pathologic processes: the β-amyloid and tau pathologies. Imaging biomarkers can reveal the natural history of the disease and show an alteration of glucose metabolism and an evolving cerebral atrophy process. The discovery of new therapies against this disease relies on early stages of drug development that can be evaluated precisely only in animals. ⋯ Animal models can also help to validate new hypotheses on disease mechanisms. We focus here on the protein misfolding hypothesis of Alzheimer as it will probably modulate our vision of the disease in forthcoming years. This hypothesis suggests that native Aβ peptides become toxic when their conformation in alpha helices evolves into a beta-sheet conformation and also suggests that misfolded proteins can transmit their misfolded conformation to normal proteins.