Co-occurrence of Alzheimer's disease β-amyloid and tau pathologies at synapses

Although beta-amyloid (A beta) plaques and tau neurofibrillary tangles are hallmarks of Alzheimer's disease (AD) neuropathology, loss of synapses is considered the best correlate of cognitive decline in AD, rather than plaques or tangles. How pathological A beta and tau aggregation relate to each other and to alterations in synapses remains unclear. Since aberrant tau phosphorylation occurs in amyloid precursor protein (APP) Swedish mutant transgenic mice, and since neurofibrillary tangles develop in triple transgenic mice harboring mutations in APP, tau and presenilin 1, we utilized these well-characterized mouse models to explore the relation between A beta and tau pathologies. We now report that pathological accumulation of A beta and hyperphosphorylation of tau develop concomitantly within synaptic terminals. (C) 2008 Elsevier Inc. All rights reserved.