Elvira De Leonibus
Institute of Genetics and Biophysics,Italy
She is the Head of Behavioral Core, TIGEM, The Neuropsychopharmacology Group, also headed by Elvira De Leonibus, applies the neurobiology of learning and memory to studies under normal and pathological conditions.
Motor symptoms in Parkinsons Disease (PD) represent the downstream effect of a pathological cascade leading to the degeneration of dopaminergic (DA) neurons of the substantia nigra compacta (SN) projecting to the striatum. Another hallmark feature of PD is late-stage occurring dementia, which is generally preceded by the occurrence of mild cognitive impairment. Mild cognitive impairment has also been shown to precede motor symptoms in PD, and therefore is considered as an early clinical marker of the pathology. The neuropathological substrate of dementia in PD patients is still under debate. Late-stage occurring dementia in PD has been associated to widespread neurodegeneration concomitant to the formation of Lewy bodies. Levy bodies are aggregates containing the synaptic protein α-synuclein (α-syn), whose accumulation is considered to be one of the major causes of neurodegeneration in PD. Accordingly, overexpression of human wild-type α-syn has been recently shown to lead to a time-dependent DA neuronal loss and motor symptoms in rats. However, the exact mechanisms through which α-syn accumulation leads to the development of dementia in PD remain unclear. By means of sites- specific adenoviral vector (AAV) mediated overexpression of human wild-type α-syn in the brain of adult mice we induced selective and severe memory impairment, which were specifically related to the function of the targeted regions. The cognitive defects observed, however, were not associated to neurodegeneration. These findings provide in vivo evidence showing that cognitive impairment precedes α-syn overexpression-mediated neurodegeneration. They suggest the interesting hypothesis that α-syn overexpression might be the cause not only of dementia occurring in the end-stage stage of PD, but also of cognitive impairment occurring in the very early stage of the disease.