Alzheimer’s disease (AD) is a multifactorial disease, and it has become a serious health problem in the world. Senile plaques (SPs) and neurofibrillary tangles (NFTs) are two main pathological characters of AD. SP mainly consists of aggregated β-amyloid (Aβ), and NFT is formed by hyperphosphorylated tau protein. Sleep–wake disorders are prevalent in AD patients; however, the links and mechanisms of sleep–wake disorders on the AD pathogenesis remain to be investigated. Here, we referred to the sleep–wake disorders and reviewed some evidence to demonstrate the relationship between sleep–wake disorders and the pathogenesis of AD. On one hand, the sleep–wake disorders may lead to the increase of Aβ production and the decrease of Aβ clearance, the spreading of tau pathology, as well as oxidative stress and inflammation. On the other hand, the ApoE4 allele, a risk gene for AD, was reported to participate in sleep–wake disorders. Furthermore, some neurotransmitters, such as acetylcholine, glutamate, serotonin, melatonin, and orexins, and their receptors were suggested to be involved in AD development and sleep–wake disorders. We discussed and suggested some possible therapeutic strategies for AD treatment based on the view of sleep regulation. In general, this review explored different views to find novel targets of diagnosis and therapy for AD.

No abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder in the central nervous system, and this disease is characterized by extracellular senile plaques and intracellular neurofibrillary tangles. Amyloid-β (Aβ) peptide is the main constituent of senile plaques, and this peptide is derived from the amyloid-β protein precursor (AβPP) through the successive cleaving by β-site AβPP-cleavage enzyme 1 (BACE1) and γ-secretase. AβPP undergoes the progress of post-translational modifications, such as phosphorylation and glycosylation, which might affect the trafficking and the cleavage of AβPP. In the recent years, about 10 phosphorylation sites of AβPP were identified, and they play complex roles in glycosylation modification and cleavage of AβPP. In this article, we introduced the transport and the cleavage pathways of AβPP, then summarized the phosphorylation and glycosylation sites of AβPP, and further discussed the links and relationship between phosphorylation and glycosylation on the pathways of AβPP trafficking and cleavage in order to provide theoretical basis for AD research.

No abstract