ABSTRACT
The extracellular accumulation and aggregation of amyloid-β (Aβ) peptides unquestionably play a major role in Alzheimer’s disease (AD) neuropathology. However, in addition to the role of extracellular Aβ, the impact of intracellular Aβ deposits in central nervous system (CNS) neurons should also be taken into account. In recent years, studies have provided evidence demonstrating the in vitro intracellular synthesis of Aβ1,2 as well as the intracellular presence of this amyloidogenic peptide in both AD-like transgenic models and human AD postmortem material.3-7 Major advances in the development of suitable cellular and transgenic animal models now allow investigations involving the differential effects of intracellular versus extracellular Aβ burden. This chapter discusses the observable effect of intracellular Aβ accumulation on protein expression and subcellular organelle organization, as well as the effect of extracellular Aβ aggregation on transmitter-specific synapses and the formation of dystrophic neurites.
