The Cellular Phase of Alzheimer’s Disease Bart De Strooper, Eric Karran  Cell  Volume 164, Issue 4, Pages 603-615 (February 2016) DOI: 10.1016/j.cell.2015.12.056 Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 Aβ Receptors and Aβ Toxicity Mechanisms All membrane receptors implied in Aβ pathogenic mechanisms are indicated. Some receptors are only indirectly affected by Aβ, inferred by physiological alterations of cells exposed to Aβ. The second series are receptors shown to directly bind Aβ (see Benilova et al., 2012). Cell 2016 164, 603-615DOI: (10.1016/j.cell.2015.12.056) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 2 The Biochemical, Cellular, and Clinical Phases of AD The transition of biochemical to cellular and cellular to clinical phases are indicated. The cellular phase is complex and evolves gradually over two decades from reversible physiological reactions upon proteopathic stress to irreversible immune and electrophysiological compensation mechanisms that disturb the normal homeostasis of the brain. The effects are cell and non-cell autonomous and occur in the context of neurovascular or glioneuronal units (see main text). Processes are derived from GWAS studies (clearance dysfunction, lipid metabolism, immune response, protein trafficking) and are indicated in different colors. Genes are in italics when genetic evidence links them to AD. Other genes (LRP1, RAGE and others) are functionally implicated in the disease process. Each gene is associated to a color code indicating the pathways in which they operate. The picture is a late self-portrait from the German painter William Utermohlen, who suffered from AD. Image courtesy of Chris Boïcos Fine Arts, Paris. Cell 2016 164, 603-615DOI: (10.1016/j.cell.2015.12.056) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 3 Molecular and Cellular Links between Astroglia and AD Astroglia are central in the cellular phase of AD. They interact directly with Aβ and display normal synaptic and metabolic responses in AD. They also display reactive and atrophic responses in AD. Major pathways are schematically represented. Cell 2016 164, 603-615DOI: (10.1016/j.cell.2015.12.056) Copyright © 2016 Elsevier Inc. Terms and Conditions