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Fig. 1 | Acta Neuropathologica Communications

Fig. 1

From: Systemic delivery of a specific antibody targeting the pathological N-terminal truncated tau peptide reduces retinal degeneration in a mouse model of Alzheimer’s Disease

Fig. 1

Pathological N-terminal tau truncation occurs in eyes of symptomatic Tg2576 mice and is successfully immunodepleted by 12A12mAb systemic delivery. a Study design. 6-month-old Tg2576 Alzheimer’s disease (AD) mice were intravenously (i.v.) injected with 12A12mAb or mouse IgG (isotype control). On day 15, mice were sacrificed and eyes were used for biochemical (Western blotting) and morphological (immunofluorescence) evaluations. Wild type (WT) mice immunized with vehicle (saline) or mouse IgG under the same experimental conditions (antibody dosage, time of treatment, administration route) were used as controls. Picture was assembled by means of Biorender online software (https://biorender.com). Western blotting analyses (b) and semi-quantitative densitometric analysis (n = 6) (c) carried out on soluble extracts from three experimental groups (wild-type, Tg2576 and Tg2576 + mAb) showing the presence of the NH2htau peptide in retina and vitreous body of Tg2576 mice and its 12A12mAb-mediated neutralization following i.v. administration. Filters were probed with three different tau antibodies reacting against different epitopes located around the extremity and middle N-terminal end of protein, including caspase-cleaved protein (CCP)-NH2 tau (26-36aa) [51, 64], BT2 (194-198aa) and DC39N1 (45-73aa). β-actin was used as loading control. Arrows on the right side indicate the molecular weight (kDa) of bands calculated from migration of standard proteins. Statistically significant differences were calculated by one-way analysis of variance (ANOVA) followed by Bonferroni’s post-hoc test for multiple comparison among more than two groups. p < 0.05 was accepted as statistically significant (*p < 0.05; **p < 0.01; ***p < 0.0005; ****p < 0.0001). D-E: Representative merged panels (d) of epifluorescent analysis (n = 4) showing the distribution of the NH2htau peptide (green channel) in retinas from three experimental groups (wild-type, Tg2576 and Tg2576 + mAb). Tissues were counterstained with DAPI (blue channel) to aid the visualization of the GCL (Ganglion Cell Layer) and INL (Inner Nuclear Layer). Haematoxylin and eosin stainings were also provided to display the cellular morphology. Histogram (e) shows that 12A12mAb immunization is effective in decreasing the NH2htau immunoreactivity in transgenic mice (**p < 0.01 versus untreated counterpart, One-way ANOVA, post-hoc Bonferroni test). Values of fluorescent intensity were expressed in arbitrary units (A.U.) Scale bar = 25 µm. Notice that, unlike not-immunized Tg2576, the GCL organization/integrity is well preserved in Tg2576 retinas following 12A12mAb treatment in correlation with a significant diminution in signal of the NH2htau

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