Affiliations: [a]
Experimental Neuropsychophysiology Lab, Santa Lucia Foundation, IRCCS, Rome, Italy
| [b] UOSD Centro Demenze, Policlinico Tor Vergata, Rome, Italy
| [c]
Department of Neuroscience and Rehabilitation, Section of Human Physiology, University of Ferrara, Italy
Correspondence:
[*]
Correspondence to: Prof. Giacomo Koch, MD PhD, Non Invasive Brain Stimulation Unit, Laboratorio di Neurologia Clinica e Comportamentale, IRCCS Fondazione S. Lucia, Via Ardeatina, 306-00179 Rome, Italy. Tel.: +39 0651501181; [email protected].
Abstract: Background:Long-term potentiation (LTP) like-cortical plasticity impairment and cholinergic neurotransmission deficits have been widely demonstrated in Alzheimer’s disease (AD) patients. Objective:In this study we aim to investigate the neurophysiological features underlying cognitive decline in AD patients according to the National Institute on Aging-Alzheimer’s Association (NIA-AA) classification and APOE genotype. Methods:65 newly diagnosed AD patients were enrolled. APOE genotype and lumbar puncture for the analysis of cerebrospinal fluid biomarkers were performed for diagnostic purposes. Patients were subdivided upon NIA-AA criteria, according to the presence of biomarkers of amyloid-β (Aβ) deposition (A) and fibrillar tau (T), in four groups: A+/T–E4 (n = 9), A+/T–E3 (n = 18), A+/T+ E4 (n = 21), and A+/T+ E3 (n = 17). We applied intermittent theta burst stimulation protocol over the primary motor cortex to assess LTP-like cortical plasticity and short latency afferent inhibition (SAI) protocol to investigate central cholinergic activity. Patients were followed over 24 months. Cognitive decline was evaluated considering changes in Mini-Mental State Examination (MMSE) scores respect to the baseline. Results:A+/T–E4 patients showed preserved LTP-like cortical plasticity as compared to A+/T–E3 and to A+/T+ patients independently from genotype (p < 0.001). In addition, A+/T–E4 patients showed a slower cognitive decline with respect to A+/T+ E4 (delta MMSE –0.5±2.12 versus –6.05±4.95; post-hoc p = 0.004) and to A+/T+ E3 patients (–4.12±4.14; post-hoc p = 0.028). No differences were found for SAI protocol (p > 0.05). Conclusion:Our results suggest that APOE4 in patients with isolated Aβ pathology could exert positive effects on LTP-like cortical plasticity with a consequent slower cognitive decline.
Keywords: Alzheimer’s disease, APOE4, dementia, isolated Aβ pathology, long-term potentiation, tau pathology, transcranial magnetic stimulation
