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, Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. samples were obtained from two Alzheimer's patients (AD1 and AD2) and one control (CTRL) individual. They were tested for several pathologies by the French reference laboratory (C. Duyckaerts, Pitié-Salpêtrière hospital
, Alzheimer samples (a-d) and the control sample (g). a One subject (AD1) displayed amyloid angiopathy. The arrowhead points to a capillary, wall of which is immunoreactive for A?. The black arrow points to a small artery with severe amyloid angiopathy, sometimes forming parenchymal deposits. b The second patient (AD2) displayed numerous senile plaques, diffuse and stellate deposits. A vessel without amyloid deposition is seen in the middle of the field (black arrows). No amyloid angiopathy was detected in that case. c-d Other sections from AD1 (c) and AD2 (d) showing amyloid plaques (black arrows). Arrow heads (in c) correspond to amyloid angiopathy. e-f, h Immunohistochemical staining, Suppl. Fig. 2 Characterization of human brain samples and homogenates. a-e Immunohistochemical staining (6F3D antibody) for A? in the two
A? 1-42 (i) A? 1-40 (j) were only detected in Alzheimer brain homogenates (20% weight/volume, ELISA). The AD1 patient that displayed more amyloid angiopathy also had more A? 1-40 than AD2. k Typical shift of tau-Cter triplets in the Alzheimer samples relative to control sample (western blot, black arrows, Acta Neuropathol Commun, vol.4, p.74, 2016. ,
, Arrow head corresponds to GAPDH loading reference. (l) Pathological pS396-positive tau smears were only detected in Alzheimer samples (western blot). Graphs display median and interquartile interval
Western blot patterns of PrPres from control (CTRL) and Alzheimer (AD) brain samples displayed no signs of PrPres pathology. T2A, PrPres type 2A control from a patient with sporadic CJD; T1, PrPres type 1 control from a patient with sporadic CJD; T2B, PrPres type 2B control from a patient with variant CJD, Ann Neurol, vol.46, pp.224-233, 1999. ,
, A? and Tau pathology in mice after inoculation with human brain homogenates. a-c Acceleration of A? deposition (arrow) in the hippocampus of an Alzheimer
, Animals inoculated with the brain presenting with amyloid angiopathy (AD1) had a higher amyloid load than the mice inoculated with the brain without angiopathy (AD2) (p = 0.01). d-f Acceleration of tau deposition in the hippocampus of an Alzheimer-inoculated Tau30 +/+ mouse (e) one month after inoculation compared to a control-inoculated mouse (d) (AT8 staining, n = 5 and 10 control-and Alzheimer-inoculated animals, respectively), APP/PS1 ?E9 mouse (b) four months after inoculation compared to a control-inoculated mouse (a) (Bam10 staining, n = 6 and 16 control-and
, Alzheimer-inoculated (h) APP/PS1 ?E9 mice four months after inoculation (n = 6 and 16 control-and Alzheimer-inoculated animals, respectively). j-l Similar Iba-1 staining in control-(j) and Alzheimer-inoculated (k), Similar GFAP staining in control-(g) and
, APP/PS1 ?E9 mice four months after inoculation (n = 6 and 16 control-and Alzheimerinoculated animals, respectively). *p < 0.05, ***p < 0.001, Mann-Whitney tests. Scale bars: main images: 500 µm
, CTRL-inoculated animals are in blue, AD1-inoculated in green and AD2-inoculated in red
, Correlation between cognitive abilities and EEG delta frequency. Delta frequency measured by EEG at 6 mpi inversely correlated with long-term memory performance (Spearman's rank correlation test). n = 6 animals per group. CTRL-inoculated animals are in blue, AD1-inoculated in green and AD2
, Time-dependent evolution of cerebral atrophy in inoculated lemurs. Rate of atrophy evolution in Alzheimer-relative to control-inoculated animals between baseline and 6 mpi (a-d), 6 mpi and 12 mpi (e-h), and 12 mpi and 18 mpi (i-l). 3D representations of atrophy rates between each time slot are, p.12
, m-p show all the time slots on the same 3D views. a-d The atrophy process was low from baseline to 6 mpi, suggesting a limited acute effect induced by Alzheimer-brain inoculation. It involved mostly the amygdala and the ventral portion of the retrosplenial cortex, mpi, orange), i (12 to 18 mpi, red)
, The group of animals inoculated with Alzheimer brains was split into those displaying tau lesions and those without tau lesions. The two tau-positive animals had the worst memory score at 18 months (a) as well as the lowest neuronal counts in the CA3 region of the hippocampus (b). CTRLinoculated animals are in blue, AD1
, Immunostaining with 4G8 in the hippocampus of Alzheimer's disease-(a-c) and control-inoculated animals (f-h) showing intracellular labelling in both groups. Quantification of intracellular labelling did not show any difference in the hippocampus (e) or in the whole brain (j). d-i shows the same staining in an Alzheimer's disease-inoculated animal in the absence of primary antibody. Intracellular structures were not detected when the primary antibody was omitted. Scale bars: 100 µm (a, f, d); 50 µm (bc, g-i). Scatter plots display median and interquartile interval, Suppl. Fig. 8 Similar level of intracellular 4G8-positive structures in Alzheimer's disease and control-inoculated lemurs