Fig. 7
DAB1 accumulates in dystrophic dendrites and axons in the CA1 region in sAD. Coronal sections of a representative (Braak stage IV, Thal phase 5) sAD case were probed with antibodies targeting ApoER2-Dab1 pathway components (see Additional file 1: Table S3). A Single-target IHC revealed that Dab1 accumulates as grape-like clusters in three layers of CA1 (stratum oriens [SO], stratum pyramidale [SP], and stratum radiatum [SR]). The globular Dab1 accumulations (open arrows in A2–4) are reminiscent of dystrophic neurites, however it is not yet clear if they are of dendritic or axonal origin. Dab1 clusters in the SP layer appear to emanate from a single neighboring neuron (black arrow in A3). A presumptive neighboring neuronal source of Dab1 complexes is not evident in the SO and SR. B MP-IHC suggested that in the SO layer Dab1 accumulates within both NFL-labeled axons (yellow arrows) and MAP2-labeled dendrites (white arrows) surrounding an ApoE enriched plaque (star). One neighboring ApoER2-expressing neuron at the SO-SP border had prominent intraneuronal accumulation of Dab1 and pTau (white arrows). Another nearby ApoER2 and Dab1-expressing neuron in the SP layer had prominent granulovacuolar co-accumulation of pP85αTyr607 and pPSD95Thr19 (open white arrows), with little or no pTauSer202/Thr205 evident. C MP-IHC in the SP layer suggested that Dab1 accumulates primarily within MAP2-labeled dendrites (white arrows in C1–4) and soma of neighboring neurons in the vicinity of extracellular ApoE (white stars). However, one Dab1-expressing globular structure co-localized with NFL (yellow arrow). Dab1 accumulated together with pTau and pPSD95Thr19 in several neighboring ApoER2-expressing neurons (white arrows in C1–4). Two nearby ApoER2 and Dab1-expressing neurons had prominent granulovacuolar co-accumulation of pP85αTyr607 and pPSD95Thr19 (open white arrows), with little or no pTauSer202/Thr205 evident. D MP-IHC in the SR layer suggested that Dab1 accumulated primarily within dystrophic NFL-labeled axons (yellow arrows in D1–4) surrounding ApoE, ApoJ and Aβ-enriched extracellular plaques (white star). Unlike the SP layer, Dab1 accumulation was not evident within MAP2-labeled dendrites. Scale bars in MP-IHC images = 10 µm