Single-target IHC using serial sections revealed that seven ApoER2-Dab1 pathway components—Dab1, pP85αTyr607, pLIMK1Thr508, pTauSer202/Thr205, pPSD95Thr19, ApoJ and ApoE—accumulated in abnormal neurons, and in proximity to NPs, were higher in MCI and sAD cases than controls and positively correlated with histological progression or antemortem cognitive deficits (Fig. 4, Additional file 1: Ext Fig. S4.1). This evidence concerns the gene APOE and Cognitive impairment.