Pre-plaque conformational changes in Alzheimer’s disease-linked Aβ and APP

Citations Over TimeTop 10% of 2017 papers

Abstract

Reducing levels of the aggregation-prone Aβ peptide that accumulates in the brain with Alzheimer's disease (AD) has been a major target of experimental therapies. An alternative approach may be to stabilize the physiological conformation of Aβ. To date, the physiological state of Aβ in brain remains unclear, since the available methods used to process brain tissue for determination of Aβ aggregate conformation can in themselves alter the structure and/or composition of the aggregates. Here, using synchrotron-based Fourier transform infrared micro-spectroscopy, non-denaturing gel electrophoresis and conformational specific antibodies we show that the physiological conformations of Aβ and amyloid precursor protein (APP) in brain of transgenic mouse models of AD are altered before formation of amyloid plaques. Furthermore, focal Aβ aggregates in brain that precede amyloid plaque formation localize to synaptic terminals. These changes in the states of Aβ and APP that occur prior to plaque formation may provide novel targets for AD therapy.

Related Papers

• → Aging Increased Amyloid Peptide and Caused Amyloid Plaques in Brain of Old APP/V717I Transgenic Mice by a Different Mechanism than Mutant Presenilin1(2000)103 cited
• → Normal cognition in transgenic BRI2-Aβ mice(2013)80 cited
• → Amyloid precursor protein increases cortical neuron size in transgenic mice(2008)72 cited
• → Proteolytical processing of mutated human amyloid precursor protein in transgenic mice(1997)36 cited
• → Phosphorylation of Amyloid Precursor Protein (APP) Family Proteins(2003)3 cited