title: Astrocytic face of Alzheimer's disease.
abstract: Ageing of the central nervous system (CNS) is the major risk factor for Alzheimer's disease (AD), a type of neurodegeneration that is associated with deficits in cognition and memory and clinically manifested as severe senile dementia. Numerous mental processes underline cognition, including attention, producing and understanding language, learning, reasoning, problem solving, decision making and memory formation. In the past, neurones or their parts have been considered to be the exclusive cellular sites of memory and cognitive processes. However, it has become evident that astrocytes, the major homeostatic glial cell of the CNS, provide an essential contribution to memory formation, and astroglial failure may promote cognitive decline in AD. In response to the network reset mechanisms mediated by the noradrenergic projections of neurones located in the locus coeruleus, astrocytes get excited and participate in the morphological remodelling associated with synaptic plasticity, otherwise thought to represent a cellular mechanism of learning and memory. Astroglial morphological plasticity is an energy-demanding process requiring mobilisation of glycogen, which, in the CNS, is almost exclusively stored in astrocytes. Astroglia exhibit cytoplasmic excitability that engages ions (such as Ca2+and Na+) and second messengers (such as cAMP). These ions/molecules contribute to the reception of extracellular signals and coordinate the secretion of glio-signalling molecules, including peptides such as apolipoporotein E, which participates in lipid transport between glia and neurones. In this setting, astrocytes are positioned as spatio-temporal integrators of neural network coordination, which disintegrates during progression of AD.
authors.affiliation: Laboratory of Neuroendocrinology and Molecular Cell Physiology, Institute of Pathophysiology, University of Ljubljana, Medical Faculty, Ljubljana, Slovenia; Celica, BIOMEDICAL, Ljubljana, Slovenia. Electronic address: robert.zorec@mf.uni-lj.si.
authors.forename: Robert
authors.initials: R
authors.lastname: Zorec
authors.affiliation: Department of Neurobiology, Civitan International Research Center and Center for Glial Biology in Medicine, Evelyn F. McKnight Brain Institute, Atomic Force Microscopy & Nanotechnology Laboratories, 1719 6th Avenue South, CIRC 429, University of Alabama at Birmingham, Birmingham, AL 35294-0021, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Parpura
authors.affiliation: Laboratory of Neuroendocrinology and Molecular Cell Physiology, Institute of Pathophysiology, University of Ljubljana, Medical Faculty, Ljubljana, Slovenia; Celica, BIOMEDICAL, Ljubljana, Slovenia.
authors.forename: Nina
authors.initials: N
authors.lastname: Vardjan
authors.affiliation: Laboratory of Neuroendocrinology and Molecular Cell Physiology, Institute of Pathophysiology, University of Ljubljana, Medical Faculty, Ljubljana, Slovenia; Celica, BIOMEDICAL, Ljubljana, Slovenia; Faculty of Life Sciences, University of Manchester, Manchester, UK; Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, Bilbao, Spain. Electronic address: alexej.verkhratsky@manchester.ac.uk.
authors.forename: Alexej
authors.initials: A
authors.lastname: Verkhratsky
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D006801:Humans; D008125:Locus Coeruleus / Q000503:physiopathology; D008568:Memory / Q000502:physiology
keywords: Alzheimer’s disease; Astroglia; Memory; Metabolism; Morphology; Vesicle traffic