title: Long-term potentiation-like cortical plasticity is disrupted in Alzheimer's disease patients independently from age of onset.
abstract: Alzheimer's disease (AD) is considered an age-related disorder. However, it is unclear whether AD induces the same pathological and neurophysiological modifications in synaptic functions independently from age of disease onset. We used transcranial magnetic stimulation tools to investigate the mechanisms of cortical plasticity and sensory-motor integration in AD patients with a wide range of disease onset.
  
  
  
  We evaluated newly diagnosed sporadic AD (n = 54) in comparison with healthy age-matched controls (HS; n = 24). Cortical plasticity mechanisms of long-term potentiation (LTP) or of long-term depression (LTD) were assessed using respectively intermittent (iTBS) or continuous theta burst stimulation (cTBS) protocols. Sensory-motor integration was evaluated by means of short afferent inhibition (SAI) protocol.
  
  
  
  AD patients show after iTBS an impairment of LTP-like cortical plasticity forming a paradoxical LTD in comparison to HS. LTD-like cortical plasticity is similar between AD and HS. LTP-like cortical plasticity is not associated with age, but AD patients presenting with more altered LTP-like cortical plasticity have more-severe cognitive decline at 18 months. SAI is impaired in AD and shows a strong association with the individual age of subjects rather than with disease age of onset.
  
  
  
  Cortical LTP disruption is a central mechanism of AD that is independent from age of onset. AD can be described primarily as a disorder of LTP-like cortical plasticity not influenced by physiological aging and associated with a more-severe cognitive decline. Ann Neurol 2016;80:202-210.
authors.affiliation: Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.|Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Lorenzo
authors.affiliation: Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Ponzo
authors.affiliation: Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Bonnì
authors.affiliation: Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.|Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Motta
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Priscilla C
authors.initials: PC
authors.lastname: Negrão Serra
authors.affiliation: Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bozzali
authors.affiliation: Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.|Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martorana
authors.affiliation: Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.|Stroke Unit, Department of Neuroscience, Tor Vergata Policlinic, Rome, Italy.
authors.forename: Giacomo
authors.identifier: 0000-0001-6155-9439
authors.initials: G
authors.lastname: Koch
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000503:physiopathology*; D016022:Case-Control Studies; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology; D050781:Transcranial Magnetic Stimulation