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Additional file 1. The additional file contains Table S1 and Figures S1-S9.

Additional file 1. Supplementary table and figures.

Table S1 Human brain sample characteristics and staging. Table S2 Schedule of the experimental protocol. Table S3 Sampling parameters for stereological counting of NeuN-positive neurons. Table S4 Brain regions with gray matter loss in the Alzheimer's disease-inoculated group relative to the control-inoculated group. Table S5 Estimated sample size to compare control and Alzheimer-inoculated mice and mouse lemurs assuming a significance level of 5%, a power of 80%, and two-sided tests. (DOCX 46 kb)

Table S1. Sequences of primers used for qPCR. (DOCX 17 kb)

Table S2. WGCNA: Top 20 most connected genes regulated by SOCS3 in APP astrocytes. Three of the top 20 hub genes, highlighted in bold, are pan or A1 reactive astrocyte genes. (DOCX 17 kb)

Table S3. Expression of phagocytic receptors and genes in astrocytes RNAseq analysis of astrocytes shows that most genes involved in Aβ phagocytosis are expressed at similar levels in all groups. Only mRNA levels for three Fc receptors are down-regulated by SOCS3. Data are presented as normalized mRNA levels +/-SEM. ## p

Alzheimer's disease is characterized by cognitive alterations, cerebral atrophy and neuropathological lesions including neuronal loss, accumulation of misfolded and aggregated β-amyloid peptides (Aβ) and tau proteins. Iatrogenic induction of Aβ is suspected in patients exposed to pituitary-derived hormones, dural grafts, or surgical instruments, presumably contaminated with Aβ. Induction of Aβ and tau lesions has been demonstrated in transgenic mice after contamination with Alzheimer's disease brain homogenates, with very limited functional consequences. Unlike rodents, primates naturally express Aβ or tau under normal conditions and attempts to transmit Alzheimer pathology to primates have been made for decades. However, none of earlier studies performed any detailed functional assessments. For the first time we demonstrate long term memory and learning impairments in a non-human primate (Microcebus murinus) following intracerebral injections with Alzheimer human brain extracts. Animals inoculated with Alzheimer brain homogenates displayed progressive cognitive impairments (clinical tests assessing cognitive and motor functions), modifications of neuronal activity (detected by electroencephalography), widespread and progressive cerebral atrophy (in vivo MRI assessing cerebral volume loss using automated voxel-based analysis), neuronal loss in the hippocampus and entorhinal cortex (post mortem stereology). They displayed parenchymal and vascular Aβ depositions and tau lesions for some of them, in regions close to the inoculation sites. Although these lesions were sparse, they were never detected in control animals. Tau-positive animals had the lowest performances in a memory task and displayed the greatest neuronal loss. Our study is timely and important as it is the first one to highlight neuronal and clinical dysfunction following inoculation of Alzheimer's disease brain homogenates in a primate. Clinical signs in a chronic disease such as Alzheimer take a long time to be detectable. Documentation of clinical deterioration and/or dysfunction following intracerebral inoculations with Alzheimer human brain extracts could lead to important new insights about Alzheimer initiation processes.