Linking Aβ and Tau in Late-Onset Alzheimer's Disease: A Dual Pathway Hypothesis  Scott A. Small, Karen Duff  Neuron  Volume 60, Issue 4, Pages 534-542 (November 2008) DOI: 10.1016/j.neuron.2008.11.007 Copyright © 2008 Elsevier Inc. Terms and Conditions

Figure 1 Two Hypothesized Models Linking Core Features of Alzheimer's Disease The amyloid hypothesis assumes a serial model of causality, whereby abnormal elevations in Aβ drive tau hyperphosphorylation and other downstream manifestations of the disease. According to the dual pathway hypothesis, Aβ elevations and tau hyperphosphorylation can be linked by separate mechanisms driven by a common upstream molecular defect. Neuron 2008 60, 534-542DOI: (10.1016/j.neuron.2008.11.007) Copyright © 2008 Elsevier Inc. Terms and Conditions

Figure 2 Anatomical Progression of Alzheimer's Disease In the typical progression of Alzheimer's disease, primary motor and sensory cortex are affected in the last stage of the disease, Braak stage VI. During the last stage of disease, the primary visual cortex is characterized by tau hyperphosphorylation (as shown using anti-phospho-tau antibodies), neurofibrillary tangles, and amyloid plaques (adapted from Braak et al., 2006 with kind permission of Springer Science/Business Media). Neuron 2008 60, 534-542DOI: (10.1016/j.neuron.2008.11.007) Copyright © 2008 Elsevier Inc. Terms and Conditions

Figure 3 Molecular Defects that Support a Dual Pathway Hypothesis in Late-Onset Disease Examples of dual pathways linking elevations of Aβ peptide and tau hyperphosphorylation through common upstream molecular defects implicated in late-onset Alzheimer's disease. Neuron 2008 60, 534-542DOI: (10.1016/j.neuron.2008.11.007) Copyright © 2008 Elsevier Inc. Terms and Conditions