In the present study in amygdala, we observed that: (1) ApoER2 is highly expressed by a subset or neurons in cognitively normal controls; (2) ApoER2 accumulates together with five of its neuronal signaling partners (Dab1, pP85αTyr607, pLIMK1Thr508, pTau Ser202/Thr205 and pPSD95Thr19) and one of its extracellular ligands (ApoJ) within abnormal neurons and extracellular plaques, respectively, in MCI and AD cases; and (3) these accumulations of ApoER2-Dab1 pathway components correlated with histological progression, cognitive deficits, and neuropsychiatric endpoints. This evidence concerns the gene CLU and Cognitive impairment.