Interestingly, synaptic spine loss in the hippocampal CA1 region (Lanz, Carter, & Merchant, 2003), changes in hippocampal long‐term potentiation (Jacobsen et al., 2006), hypersynchrony of neuronal network activity (Shah et al., 2016), and cognitive impairment (King & Arendash, 2002) were reported at 4–6 months of age, indicating the importance of soluble neurotoxic Abeta assemblies or of intracellular APP C‐terminal fragments (Xu, Fitzgerald, Nixon, Levy, & Wilson, 2015) present before amyloid plaque pathology. Here, APP is linked to Cognitive impairment.