Fig. 9

Dab1 accumulates together with ApoER2 signaling partners in temporal cortex in MCI and sAD. A Serial coronal sections of the temporal neocortex from representative 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). In the non-sAD control (A), single-target IHC revealed that Dab1 expression is confined to a subset of pyramidal neurons (solid arrows). In MCI (B) and sAD (C) cases, prominent accumulations of Dab1 were observed within abnormal neurons and within clusters of globular structures (open arrows in B and C) in the vicinity of NPs (black stars) that in some cases appeared to emanate from neighboring neurons (black arrows in A_3–4, A_9–10, C_1–2). Intraneuronal Dab1 inclusions are evident in a subset of L3 and L5 pyramids (solid arrow C4); neighboring neurons with little or no Dab1 expression are designated with an * in C₄. D Dab1 accumulation increased across the clinicopathological spectrum of sAD and correlated with pPSD95_Thr19, Braak stage, Aβ plaque load, and cognitive deficits. In the dot plot, 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 value is from a Kruskal–Wallis test. Fitted line plots show Spearman’s rank correlation coefficients and p values. E MP-IHC suggested that Dab1, pTau_{Ser202/Thr205} and pPSD95_Thr19 accumulate within the same ApoER2-expressing, NFT-bearing L5 and L3 pyramids (yellow arrows in E_1–5) and MAP2-labeled dystrophic dendrites (yellow arrows in E_6–10) in the immediate vicinity of Aβ plaques with ApoE enriched in the central core (white stars in E_6–10). A small portion of Dab1 deposits appeared to accumulate within NFL-labeled axons or synaptophysin-labeled presynaptic terminals (white arrows in E_9–10). Scale bars in MP-IHC images = 10 µm