LTP-Like Plasticity is Impaired in Amyloid-Positive Amnestic MCI But Independent of PET-Amyloid Burden


Neurobiology of Aging. 96:109-116, 2020 12.

Buss SS; Press DZ; McDonald K; Kitchener E; O’Connor M; Donohoe K; Shafi MM; Pascual-Leone A; Fried PJ

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.