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.