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[Preprint]. 2023 Nov 13:2023.07.01.547348. [Version 3] doi: 10.1101/2023.07.01.547348

Figure 2. Neuropathologic evaluation demonstrates high Alzheimer disease pathologic change (ADNC) by NIA-AA criteria in SORL1 R953C cases.

Figure 2.

(a) Representative section of cerebellum stained for β-amyloid (6e10), highlighting plaques within the molecular layer and warranting a Thal phase 5. Patient II-5, scale bar = 50 μm. (b) Representative section of calcarine cortex stained for phosphorylated tau (P-Tau; AT8), highlighting neurofibrillary tangles in a background of dystrophic neurites, consistent with Braak and Braak stage VI. Patient II-5, scale bar = 20 μm. (c) Representative section of middle frontal gyrus stained with Bielschowsky silver demonstrating frequent neuritic plaques by CERAD criteria. Insert shows a representative neuritic plaque, composed of brown, targetoid β-amyloid associated with black dystrophic neurites. Patient II-5, scale bars = 50 μm. (d) Representative section of hippocampus stained for phosphorylated TDP-43 (P-TDP43), demonstrating intracytoplasmic inclusions and scattered dystrophic neurites. The pattern is consistent with limbic-predominant age-related TDP-43 encephalopathy (LATE) stage 2, though age < 80 years is atypical for sporadic LATE. Patient II-4, scale bar = 20 μm. (e) Representative section of anterior cingulate gyrus stained for α-synuclein, highlighting the presence of a Lewy body in a background of positive neurites. Though Lewy body disease was present in the majority of SORL1 R953C carriers, the pattern was highly variable. Patient II-2, scale bar = 20 μm.