title: The role of astrocytes in amyloid β-protein toxicity and clearance.
abstract: The deposition of the amyloid β-protein (Aβ) in the brain is a pathological hallmark of Alzheimer's disease (AD). Here, Aβ deposits occur as Aβ plaques in the brain parenchyma and in the walls of cerebral and leptomeningeal blood vessels. Astrocytes are considered to be involved in the clearance of Aβ from the brain parenchyma into the perivascular space, across the blood-brain barrier, or by enzymatic degradation. As such it has been assumed that clearance of Aβ by astrocytes is beneficial. In a recent study published in Experimental Neurology Mulder et al. (2012; 233: 373-379) report changes in neprilysin and scavenger receptor class B member 1 gene expression in astrocytes exposed to fibrillar Aβ depending on the availability of amyloid-associated proteins, especially apolipoprotein E (apoE). Astrocytes from AD patients did not show this response in gene expression. Reactive astrocytes and Aβ containing astrocytes are common findings in the AD brain. A loss of excitatory amino acid transporter 2 expression in perivascular astrocytes of APOE ε4-positive AD cases and an alteration of neuronal apoE metabolism in the event of perivascular drainage of apoE-Aβ complexes has also been described. As such, reactive and compensatory changes in AD astrocytes compete with supporting functions of astrocytes finally leading to an impairment of metabolic support and transmitter recycling in the brain. In summary, exposure of astrocytes to increased amounts of Aβ over a long period in time very likely impairs the above mentioned supporting functions of astrocytes in AD patients because these cells have to clear large amounts of Aβ and, thereby, neglect their other functions.
authors.affiliation: Institute of Pathology, Laboratory of Neuropathology, Center for Biomedical Research, University of Ulm, Helmholtzstr. 8/1, D-89081 Ulm, Germany. Dietmar.Thal@uni-ulm.de
authors.forename: Dietmar Rudolf
authors.initials: DR
authors.lastname: Thal
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments