Fig. 4

Multiple ApoER2-Dab1 pathway components accumulate together with pTau in ErC in MCI and sAD cases. A Serial coronal sections of the entorhinal region from non-AD control (Braak stage I), MCI (Braak stage III) and sAD (Braak stage VI) cases were probed with antibodies targeting ApoER2-Dab1 pathway components (see Additional file 1: Table S3). Zoomed-out images of the non-sAD control are provided (left column in A) to illustrate the lack of positive IHC staining throughout the whole ErC section, with only modest pTau_{Ser202/Thr205} accumulation (open arrows in A₂) and no overt accumulation of pP85α_Tyr607, pLIMK1_Thr508, or pPSD95_Thr19. Dab1 expression was confined to the soma of a subset of neurons. By contrast, in MCI (middle column in A) and especially sAD (right column in A), prominent accumulations of pTau_{Ser202/Thr205}, Dab1, pP85α_Tyr607, pLIMK1_Thr508, and pPSD95_Thr19 were observed within abnormal neurons (solid arrows) and in the vicinity of NPs (black stars). Examples of neighboring neurons with little or no evidence of ApoER2-Dab1 component accumulation are designated with * (A_4,15,22,27). Open arrows in A₁₇ and A_22–23 designate granulovacuolar accumulations of pP85α_Tyr607 and pLIMK1_Thr508, respectively. B The expression of multiple neuronal ApoER2-Dab1 pathway components increased across the clinicopathological spectrum of sAD (B_1–3,6–8) and correlated with Braak stage (B_4,9) and cognitive deficits (B_9,10). For dot plots, open and closed blue circles indicate young controls and age-matched controls; open and closed red diamonds indicate MCI cases and sAD cases, respectively. p values are from Kruskal–Wallis tests. Fitted line plots show Spearman’s rank correlation coefficients and p values. C MP-IHC suggested that Dab1, pTau_{Ser202/Thr205}, and pPSD95_Thr19 accumulate together within ApoER2-expressing neurons (white arrows in C_1–4) and that Dab1 accumulated within MAP2-labeled dystrophic dendrites (yellow arrows in C_1–4) in the vicinity of ApoE and ApoJ-enriched extracellular plaques (white star). Scale bars in MP-IHC images = 5 µm