Intraneuronal ß-amyloid and its interactions with proteins and subcellular organelles.

Amyloidogenic aggregation and misfolding of proteins are linked to neurodegeneration. The mechanism of neurodegeneration in Alzheimer's disease, which gives rise to severe neuronal death and memory loss, is not yet fully understood. The amyloid hypothesis remains the most accepted theory for the pathomechanism of the disease. It was suggested that ß-amyloid accumulation may play a key role in initiating the neurodegenerative processes. The recent intracellular ß-amyloid (iAß) hypothesis emphasizes the primary role of iAß to initiate the disease by interaction with cytoplasmic proteins and cell organelles, thereby triggering apoptosis. Sophisticated methods (proteomics, protein microarray, and super resolution microscopy) have been used for studying iAß interactions with proteins and membraneous structures. The present review summarizes the studies on the origin of iAß and the base of its neurotoxicity: interactions with cytosolic proteins and several cell organelles such as endoplasmic reticulum, endosomes, lysosomes, ribosomes, mitochondria, and the microtubular system.