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Fig. 6 | Acta Neuropathologica Communications

Fig. 6

From: ApoER2-Dab1 disruption as the origin of pTau-associated neurodegeneration in sporadic Alzheimer’s disease

Fig. 6

Co-accumulation of ApoER2-Dab1 pathway components in ProS-CA1 border region in sAD. (A) Serial coronal sections of the ProS-CA1 region from representative non-AD control (Braak stage I) and sAD (Braak stage IV) 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 little or no expression of pTauSer202/Thr205 and pPSD95Thr19, with modest Dab1 expression confined to a subset of neurons. In sAD cases, pTauSer202/Thr205 accumulated within NTs, NFTs, and the neuritic components of NPs (B1–5). Dab1 accumulated within abnormal neurons (B7–8) and in plaque-associated clusters of globular neurites (B8–10). pPSD95Thr19 accumulated within abnormal neurons, neuritic components of NPs, and in discrete punctae within the neuropil. All three components accumulated within the apical stripe region (arrows in B1,6&11), which harbors the terminal apical dendritic projections emanating from basal ProS-CA1 pyramidal neurons. C Expression of Dab1, pTauSer202/Thr205, pPSD95Thr19, pP85αTyr607, pLIMK1Thr508, pDab1Tyr220, ApoE, and ApoJ increased across the clinicopathological spectrum of sAD and correlated with Braak stage and cognitive deficits (C1–15). 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. IHC images for pP85αTyr607, pLIMK1Thr508, pDab1Tyr220, and ApoJ are provided in Additional file 1: Ext Fig. S6.1

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