Long-term potentiation-like cortical plasticity is disrupted in Alzheimer's disease patients independently from age of onset

Di Lorenzo, Francesco, Ponzo, Viviana, Bonnì, Sonia, Motta, Caterina, Negrão Serra, Priscilla C, Bozzali, Marco, Caltagirone, Carlo, Martorana, Alessandro and Koch, Giacomo (2016) Long-term potentiation-like cortical plasticity is disrupted in Alzheimer's disease patients independently from age of onset. Annals of neurology, 80 (2). pp. 202-210. ISSN 1531-8249

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Abstract

OBJECTIVE
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.

METHODS
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.

RESULTS
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.

INTERPRETATION
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.

Item Type: Article
Additional Information: IF= 9.46
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
Subjects: R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
Depositing User: Patricia Butler
Date Deposited: 06 Dec 2019 13:58
Last Modified: 11 Dec 2019 10:02
URI: http://sro.sussex.ac.uk/id/eprint/72904

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