TMS can detect abnormal synaptic plasticity associated with amyloid-beta and tau pathology in early staged dementia

T. Murakami, M. Abe, A. Tiksnadi, N. Kobayashi, Y. Hashimoto, Y. Ugawa

Research output: Contribution to journalArticlepeer-review


Amyloid-beta (Aβ) and phosphorylated-Tau (pTau) proteins in cerebrospinal fluids (CSF) are known as the most reliable biomarker for early and preclinical staged Alzheimer’s disease (AD).
The aim of this study is to investigate relationship between these biochemical biomarkers and the impairment of synaptic plasticity studied with transcranial magnetic quadripulse stimulation (QPS) in patients with early staged dementia.
Eighteen patients with dementia; 9 early AD and 9 amnesic mild cognitive impairment (aMCI), and 10 age-matched subjects with normal cognition (NC) participated in this study. Aβ (Aβ40, Aβ42) and pTau proteins were measured from the sampled CSF. Subjects were classified into three subgroups; Aβ40/42-ratio negative, pTau negative (N/N), Aβ40/42-ratio positive, pTau negative (P/N), and both positive (P/P). Facilitatory QPS5 was given over the left primary motor cortex hand area. Single-pulse transcranial magnetic stimulation (TMS) was applied over the left motor hand area and motor-evoked potentials (MEP) were recorded from the right first-dorsal interosseous muscle before and after QPS5.
Eight NC subjects were in the N/N, and 2 were in the P/N. Four aMCI and 4 early AD were in the P/N. Five aMCI and 5 AD were in the P/P. The P/N subjects had no LTP-like synaptic plasticity, while QPS5 successfully induced the LTP-like plasticity in the N/N. The synaptic plasticity was reversed to the depression in the P/P. Correlation analysis revealed that the magnitude of QPS5-induced MEP changes correlated negatively with Aβ40/42-ratio and pTau. Our findings indicate that accumulation of Aβ is associated with reduction of the LTP-like plasticity. Depression of synaptic plasticity in pTau positive group may reflect neurotoxicity of Tau phosphorylation leading to neuronal cell death. The synaptic plasticity evaluated by TMS may be a useful biomarker of the functional decline in early staged dementia.
Original languageEnglish
Pages (from-to)398
JournalBrain Stimulation
Issue number2
Publication statusPublished - 1 Mar 2019


  • amyloid-beta, phosphorylated Tau, synaptic plasticity, transcranial magnetic stimulation


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