LTP-like plasticity is impaired in amyloid-positive amnestic MCI but independent of PET-amyloid burden

Neurobiol Aging. 2020 Dec:96:109-116. doi: 10.1016/j.neurobiolaging.2020.08.021. Epub 2020 Sep 3.

Abstract

Transcranial magnetic stimulation (TMS) reveals decreased efficacy of long-term potentiation-like (LTP-like) neuroplastic mechanisms in Alzheimer's disease (AD). However, it is not yet known whether LTP-like plasticity is also impaired in prodromal AD, or how abnormal TMS measures are related to established AD biomarkers. Here, we investigated the LTP-like response to intermittent theta-burst stimulation in 17 amyloid-positive participants with amnestic mild cognitive impairment (MCI) and 10 cognitively unimpaired controls. Our results showed a lack of LTP-like neuromodulation in MCI compared with controls that was unrelated to quantitative amyloid-beta burden on positron emission tomography. Surprisingly, greater LTP-like response was related to worse memory function in the MCI group, highlighting the complex role of neuroplasticity in the prodromal stages of AD. Overall, our results demonstrate abnormal LTP-like plasticity using intermittent theta-burst stimulation assessment in amyloid-positive participants with MCI. These findings support the potential for development of TMS measures as prognostic markers or therapeutic targets in early-stage symptomatic AD.

Keywords: Alzheimer's disease; Amyloid; Mild cognitive impairment; Plasticity; Transcranial magnetic stimulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / etiology
  • Amyloid beta-Peptides / metabolism*
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / physiopathology*
  • Cognitive Dysfunction / psychology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Long-Term Potentiation / physiology*
  • Male
  • Memory
  • Middle Aged
  • Neuronal Plasticity / physiology*
  • Positron-Emission Tomography
  • Prospective Studies
  • Transcranial Magnetic Stimulation

Substances

  • Amyloid beta-Peptides