Evaluation of sleep deprivation effects on function and metabolism of amyloid-beta peptides

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease that exhibits important hallmarks as a progressive cognitive decline and the commitment of elderly people. This disease has a significant impact on the mortality rate and the global economy. Despite the efforts made by research groups around the world, the cure for AD has not yet been discovered and the scarce treatment alternatives are only aimed in delaying its progression. It is known that the main molecular characteristics presented by AD patients are the presence of both neurofibrillary tangles composed by tau protein and senile plaques formed by aggregates of amyloid-beta peptide (pAbeta). Another observation in these patients is a higher prevalence of epsilon-4 allele that codifies the E4 isoform of apolipoprotein E (apoE). Moreover, there is a direct relationship between AD and aspects related to sleep. Individuals with this disease usually present alterations in sleep profile. On the other hand, sleep deprivation may also be considered a risk factor for the development of AD, since lack of sleep causes accumulation of pAbeta in the brain. This accumulation may be related to the activity exerted by apoE on the pAbeta metabolism. Once pAbeta accumulates, they can trigger neurotoxic signals via cellular prion protein (PrPC) and group I metabotropic glutamate receptor (mGluRI). However, Laminin (LN) can also bind to PrPC-mGluRI and generate an opposite response. Our previous results showed that pAbeta can compete with LN for binding to PrPC. Therefore, this study aims to evaluate the effects of pAbeta accumulation on neuritogenesis process triggered by the interaction between PrPC-LN and verify the role of apoE in the pAbeta accumulation induced by sleep deprivation. Understanding the effects of sleep deprivation on function and metabolism of pAbeta may help to elucidate the mechanisms of AD pathogenesis and also contribute to the creation and improvement of treatments in order to reduce the mortality rates and expenses generated by this dementia. (AU)