Cholesterol dysmetabolism in Alzheimer’s disease: A starring role for astrocytes?

In recent decades, the impairment of cholesterol metabolism in the pathogenesis of Alzheimer's disease (AD) has been intensively investigated, and it has been recognized to affect amyloid β (Aβ) production and clearance, tau phosphorylation, neuroinflammation and degeneration. In particular, the key role of cholesterol oxidation products, named oxysterols, has emerged. Brain cholesterol metabolism is independent from that of peripheral tissues and it must be preserved in order to guarantee cerebral functions. Among the cells that help maintaining brain cholester-ol homeostasis, astrocytes play a starring role since they deliver de novo synthesized cholesterol to neurons. In addition, other physiological roles of astrocytes are to modulate synaptic trans-mission and plasticity and support neurons providing energy. In the AD brain, astrocytes un-dergo significant morphological and functional changes that contribute to AD onset and devel-opment. However, the extent of this contribution and the role played by oxysterols are still un-clear. Here we review the current understanding on the physiological role exerted by astrocytes in the brain and their contribution to AD pathogenesis. In particular, we focus on the impact of cholesterol dysmetabolism on astrocyte functions suggesting new potential approaches to de-velop therapeutic strategies aimed at counteracting AD development.