Glia cells, lipid metabolism and Alzheimer's disease

Research on functioning of the central nervous system (CNS) has mainly focused on neurons alone. Glia cells, which far outnumber neurons in the brain, were thought to support those neuronal functions and were considered to be less important. However, intense research has revealed the true role of glia cells in the CNS, which include homeostasis maintenance, providing feedback to neurons and regulation of synaptic plasticity. Astrocytes, the most abundant glia cells, are involved in brain lipid metabolism as they secrete Apolipoprotein E (ApoE), the main lipid carrier in the brain, and express lipoprotein receptors involved in the uptakeof lipids. The human ApoE exists in three isoforms of which the ApoE4 isoform is associated with an increased risk of developing Alzheimer’s disease (AD). Furthermore, epidemiological studies revealed that patients with hypercholesterolemia that were treated with cholesterol lowering drugs also had a reduced risk of developing AD. This implicates that lipid metabolism might contribute to AD pathogenesis. Together with the important role of astrocytes in regulating this lipid metabolism, this suggests that astrocytes might contribute to the pathogenesis of AD, although they are not causative for its onset