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

Francesco Di Lorenzo, Viviana Ponzo, Sonia Bonnì, Caterina Motta, Priscilla C. Negrão Serra, Marco Bozzali, Carlo Caltagirone, Alessandro Martorana, Giacomo Koch

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)202-210
Number of pages9
JournalAnnals of Neurology
Volume80
Issue number2
DOIs
Publication statusPublished - Aug 1 2016

Fingerprint

Age of Onset
Alzheimer Disease
Long-Term Potentiation
Depression
Transcranial Magnetic Stimulation

ASJC Scopus subject areas

  • Medicine(all)
  • Neurology
  • Clinical Neurology

Cite this

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; Koch, Giacomo.

In: Annals of Neurology, Vol. 80, No. 2, 01.08.2016, p. 202-210.

Research output: Contribution to journalArticle

@article{32f789e24e1c4344924d5c7edf484355,
title = "Long-term potentiation–like cortical plasticity is disrupted in Alzheimer's disease patients independently from age of onset",
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.",
author = "{Di Lorenzo}, Francesco and Viviana Ponzo and Sonia Bonn{\`i} and Caterina Motta and {Negr{\~a}o Serra}, {Priscilla C.} and Marco Bozzali and Carlo Caltagirone and Alessandro Martorana and Giacomo Koch",
year = "2016",
month = "8",
day = "1",
doi = "10.1002/ana.24695",
language = "English",
volume = "80",
pages = "202--210",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

TY - JOUR

T1 - Long-term potentiation–like cortical plasticity is disrupted in Alzheimer's disease patients independently from age of onset

AU - Di Lorenzo, Francesco

AU - Ponzo, Viviana

AU - Bonnì, Sonia

AU - Motta, Caterina

AU - Negrão Serra, Priscilla C.

AU - Bozzali, Marco

AU - Caltagirone, Carlo

AU - Martorana, Alessandro

AU - Koch, Giacomo

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84981294804&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84981294804&partnerID=8YFLogxK

U2 - 10.1002/ana.24695

DO - 10.1002/ana.24695

M3 - Article

C2 - 27255833

VL - 80

SP - 202

EP - 210

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 2

ER -