Disrupted sleep is a major feature of Alzheimer’s disease (AD), and it usually appears years before symptoms of cognitive decline emerge.
It seems prolonged wakefulness aggravates the production of amyloid-beta (Aβ) species, which is a major driver of AD progression.
This sleep loss tends to further accelerate AD, with this tendency becoming a vicious cycle of sleepiness and AD advancement.
Unfortunately, the mechanisms by which Aβ affects sleep are still unknown and reason for much research.
Recently, Özcan and team of researchers have shown that in zebrafish, Aβ acutely and reversibly can enhance or suppress sleep in the fish as a function of the length of the oligomer, that is the number of Aβ molecules bounded together.
Genetic disruption analysis has shown that short Aβ oligomers induce acute wakefulness through Adrenergic receptor b2 (Adrb2) and Progesterone membrane receptor component 1 (Pgrmc1). While longer Aβ forms, can actually induce sleep through a pharmacologically tractable Prion Protein (PrP) signalling cascade.
What this data shows, is that Aβ can actually trigger a bi-directional sleep/wake switch in the zebrafish.
And, what this could mean, is that alterations to the brain’s Aβ oligomeric environment, such as during the progression of AD, may lead to disrupt sleep through changes in acute signalling events through similar receptors.