Current treatment options for patients with Alzheimer’s disease (AD) are limited at providing symptomatic relief, with no effects on the underlying pathophysiology. Recently, advances in the understanding of the AD pathogenesis highlighted the role of ABeta (Aβ) oligomers particularly interfering with mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD). These findings led to the development of potential anti-amyloid therapies, and among them homotaurine, a glycosaminoglycan mimetic designed to interfere with the actions of Aβ early in the cascade of amyloidogenic events, and by its γ-aminobutyric acid type (GABA) A receptor affinity. Recently, we showed that AD patients have impaired LTP-like cortical plasticity, as measured by standard theta burst stimulation protocols applied over the primary motor cortex (M1). Furthermore, AD patients have a weakened short latency afferent inhibition (SLAI), a neurophysiological measure of central cholinergic transmission, which changes reflect the cholinergic dysfunction occurring in the pathology. Here, we aimed at investigating whether homotaurine administration could modulate in vivo measured mechanisms of synaptic plasticity, namely LTP and LTD, and also SLAI in a group of mild cognitive impaired patients. We observed that homotaurine administration did not induce relevant changes of both LTP and LTD recordings, while induced changes of SLAI in our group of patients. We suggest that homotaurine effects are dependent on changes of cortical GABA transmission suggesting a potential role for this compound in ameliorating the cholinergic transmission by modulating the inhibitory cortical activity.

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Nineteen non‐demented Parkinson's disease patients have been studied before and during L‐dopa therapy by quantitative EEG performed at rest with eyes closed (EC) and during attentive (BR) and cognitive (FIX) tasks. The data have been compared by ANOVA analysis with those of 22 age‐matched healthy subjects. In all three conditions a significant increase of the mean δ power as well as a decrease of β1 power was observed in patients before therapy. Abnormal high δ values were observed in 10 out of 19 patients. L‐Dopa therapy did not modify this EEG pattern. After therapy, however, a significant decrease of reactivity to BR and FIX was observed in patients compared to normal subjects. These data confirmed the presence of an EEG synchronization (increase of slow activity and decrease of fast activity) in non‐demented Parkinson's disease patients. This pattern, similar to that of subjects with Alzheimer‐type dementia, might indicate an intellectual impairment at sub‐clinical level. A non‐dopaminergic mechanism could be responsible for this impairment