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

• Published in: Clinical neurophysiology 2024-02, Vol.158, p.170-179
• Main Authors: Murakami, Takenobu, Abe, Mitsunari, Tiksnadi, Amanda, Nemoto, Ayaka, Futamura, Miyako, Yamakuni, Ryo, Kubo, Hitoshi, Kobayashi, Naoto, Ito, Hiroshi, Hanajima, Ritsuko, Hashimoto, Yasuhiro, Ugawa, Yoshikazu
• Format: Article
• Language: English
• Subjects: Alzheimer’s disease; Amyloid beta; Long-term potentiation; Quadripulse stimulation; Synaptic plasticity; Tau; Transcranial magnetic stimulation
• ISSN: 1388-2457; 1872-8952
• DOI: 10.1016/j.clinph.2023.12.131

•The degree of LTP-like plasticity was correlated with amyloid and tau biomarkers.•The degree of LTP-like plasticity was correlated with cognitive function.•NBS techniques using QPS5 can be used as a neurophysiological biomarker for cognitive decline related to AD pathology. 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. 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) with11C-Pittsburg compound-B was also conducted. We studied correlations of QPS5-induced plasticity with cognitive functions or AD-related biomarkers. 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. 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. Assessing motor-cortical plasticity could be a useful neurophysiological biomarker for AD pathology.