Effects of homotaurine on DLPFC disarray in MCI and the role of GABA: Human/Human trials: Nutraceuticals and non‐pharmacological interventions. (7th December 2020)

• Record Type: Journal Article
• Authors: Bonomi, Chiara Giuseppina; De Lucia, Vincenzo; Motta, Caterina; Koch, Giacomo; Martorana, Alessandro
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 9
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.043257
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Homotaurine has been studied for its capacity to interact with amyloid‐beta monomers preventing their aggregation to oligomers, which carry a high degree of synaptic toxicity and are thought to play an upstream role in the pathogenesis of Alzheimer's disease (AD)1. At once, this compound directly modulates excitatory neurotransmission via its high affinity with GABA‐A receptors. A recent study showed that homotaurine improves cholinergic transmission, likely by modulating inhibitory cortical activity2. Its anti‐amyloid properties combined with the GABAergic profile make homotaurine a new potential drug for the treatment of AD. Since pathological changes long precede cognitive decline in AD, Mild Cognitive Impairment (MCI) should be looked upon as a favoured stage for interventions aimed at stopping or slowing the progression of the disease. Several neurophysiological studies also highlighted that, from the earliest stages of AD, cortical plasticity at the dorso‐lateral Pre‐Frontal Cortex (dlPFC) is impaired, with lost of physiological beta‐gamma oscillatory response to TMS. We decided to test the effects of homotaurine on dlPFC functionality in patients with MCI. Method: We used TMS‐EEG to non‐invasively stimulate the left and right dlPFC of 5 patients that accessed to our Memory Clinic for subjective amnestic impairment (mean MMSE 28). Registration was performed at baseline and after 15 days of treatment with Tramiprosate 100 mg/day. Result: At baseline, the response on left dlPFC was weak in frequency, with an anomalous spot on lower alpha frequencies. Instead, the stimulation on right dlPFC originated a powerful response, yet aspecific in frequency, outlining a prominent inter‐hemispheric asymmetry. Post treatment results showed (1) a spectrum of oscillation frequency more coherent with physiological registrations and (2) interhemispheric symmetry in response. Conclusion: These data suggest that Homotaurine increases frequency of oscillation in dlPFC, and helps re‐establishing, at least partially, interhemispheric balance in terms of oscillation in patients with amnestic impairment. This rapid effect likely depends on Homotaurine‐mediated changes of cortical GABA transmission, meaning that GABA might be implicated in cortical disarray from the earliest stages of AD.