Abnormal motor cortical plasticity as a useful neurophysiological biomarker for Alzheimer's disease pathology

Takenobu Murakami, Mitsunari Abe, Amanda Tiksnadi, Ayaka Nemoto, Miyako Futamura, Ryo Yamakuni, Hitoshi Kubo, Naoto Kobayashi, Hiroshi Ito, Ritsuko Hanajima, Yasuhiro Hashimoto, Yoshikazu Ugawa

Research output: Contribution to journalArticlepeer-review


Objective: Amyloid-beta (Aβ) and tau accumulations impair long-term potentiation (LTP) induction in animal hippocampi. We investigated relationships between motor-cortical plasticity and biomarkers for Alzheimer's disease (AD) diagnosis in subjects with cognitive decline. Methods: Twenty-six consecutive subjects who complained of memory problems participated in this study. We applied transcranial quadripuse stimulation with an interstimulus interval of 5 ms (QPS5) to induce LTP-like plasticity. Motor-evoked potentials were recorded from the right first-dorsal interosseous muscle before and after QPS5. Cognitive functions, Aβ42 and tau levels in the cerebrospinal fluid (CSF) were measured. Amyloid positron-emission tomography (PET) with 11C-Pittsburg compound-B was also conducted. We studied correlations of QPS5-induced plasticity with cognitive functions or AD-related biomarkers. Results: QPS5-induced LTP-like plasticity positively correlated with cognitive scores. The degree of LTP-like plasticity negatively correlated with levels of CSF-tau, and the amount of amyloid-PET accumulation at the precuneus, and correlated with the CSF-Aβ42 level positively. In the amyloid-PET positive subjects, non-responder rate of QPS5 was higher than the CSF-tau positive rate. Conclusions: Findings suggest that QPS5-induced LTP-like plasticity is a functional biomarker of AD. QPS5 could detect abnormality at earlier stages than CSF-tau in the amyloid-PET positive subjects. Significance: Assessing motor-cortical plasticity could be a useful neurophysiological biomarker for AD pathology.

Original languageEnglish
Pages (from-to)170-179
Number of pages10
JournalClinical Neurophysiology
Publication statusPublished - Feb 2024


  • Alzheimer's disease
  • Amyloid beta
  • Long-term potentiation
  • Quadripulse stimulation
  • Synaptic plasticity
  • Tau
  • Transcranial magnetic stimulation


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