Simple model systems: a challenge for Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia. This incurable, degenerative, and terminal disease is usually diagnosed in people over 65 years of age, although the less-prevalent early-onset AD can occur much earlier. The morphologic features observed in AD patients at autopsy include both extracellular amyloid deposits as amyloid senile plaques and intracellular neurofibrillary tangles (NFT). The main constituent of the amyloid deposits is an amphiphilic peptide, derived by proteolysis from a large membrane spanning precursor protein, the amyloid precursor protein (APP). According to the amyloid hypothesis cascade, the beta-amyloid (Aβ) peptide deposits are the fundamental cause of the disease [1]. Depending on cellular conditions, Aβ is misfolded and the establishment of Aβ conformations, prone to self-assembling, could represent a key point of the neurodegenerative process. The intermolecular aggregation, prompted by instability, strongly correlates to the increase of ordered structures rich of beta-sheets, typical of amyloid assemblies. Fibrillar forms of Aβ found in amyloid plaques were previously considered the major cause of neuronal damage in AD, but recently it has been discovered that the Aβ soluble oligomers, also known as Aβ-derived diffusible ligands (ADDLs), are the more potent neurotoxins [2]. Another AD hallmark are the NFT, composed by neurofilaments and hyperphosphorylated tau protein, a microtubule associated polypeptide. These two markers are common both to late-onset/sporadic AD and early-onset/familial AD (FAD) suggesting a common pathogenic pathway [3]. However, it is not yet well clear, if the presence of these two hallmarks is the cause or the effect of a cascade of events including oxidative stress, mitochondrial damage and death for apoptosis. A scheme of these events is showed in Figure 1.A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation t