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

Abstract Transcranial magnetic stimulation (TMS) reveals decreased efficacy of long-term potentiation-like (LTP-like) plasticity 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 (iTBS) in 17 amyloid-positive amnestic mild cognitive impairment (MCI) participants and 10 cognitively unimpaired controls. Our results showed a lack of LTP-like effect in MCI compared to controls that was unrelated to quantitative Aβ burden on PET. 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 iTBS assessment in amyloid-positive MCI participants. These findings support the potential for development of TMS measures as prognostic markers or therapeutic targets in early-stage symptomatic AD.