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Fig. 5 | Acta Neuropathologica Communications

Fig. 5

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

Fig. 5

Multiple ApoER2-Dab1 components accumulate in the same ApoER2-expressing ErC L2 neurons in Braak stage I. Serial coronal sections of the ErC from one non-AD control case in an initial stage of NFT pathology (Braak stage I, Thal phase I, MMSE 27/30) were probed with antibodies targeting ApoER2-Dab1 pathway components. Single-target IHC revealed that both stellate-shaped (designated S) and pyramid-shaped (designated P) neurons in ErC L2 strongly express ApoER2 (A1–5), and that multiple ApoER2-Dab1 pathway components including Dab1 (A6–10), pP85αTyr607 (A10–11), pLIMK1Thr508 (A12–15), and pPSD95Thr19 (A21–25) accumulated together with pTauSer202/Thr205 (A16–20). Dab1 accumulated within the soma of a subset of ErC L2 neurons (solid arrows) and adjacent globular grape-like structures (open arrows). pP85αTyr607 accumulated within the soma of a subset of stellate-shaped neurons (S in A11). pLIMK1Thr508 accumulated within a subset of stellate-shaped (S in A12–13) and pyramidal neurons (P in A12). Granulovacuolar pLIMK1Thr508 accumulations are designated with solid arrows in A14. pTauSer202/Thr205 accumulated within a subset of NFT-bearing stellate-shaped and pyramidal neurons, and as NTs in the adjacent neuropil. pPSD95Thr19 accumulated in the soma of affected stellate-shaped and pyramidal neurons and as discrete punctae in adjacent neuropil. Neighboring neurons with little or no evident accumulations of ApoER2-Dab1 components are designated with an * in A10–25. B MP-IHC suggested that pTauSer202/Thr205, Dab1, pLIMK1Thr508, and pPSD95Thr19 accumulate together within the same ApoER2-expressing stellate-shaped neurons (designated S in B1–5) and pyramidal neurons (designated P in A5–8), and adjacent dystrophic neurites (yellow arrows) that may emanate from these abnormal ApoER2 and Dab1-expressing ErC L2 neurons. Neighboring NEUN-labeled neurons with little or no ApoER2-Dab1 components evident in the soma are designated with an *. Scale bars in MP-IHC images = 5 µm

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