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

Abstract

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) with¹¹C-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.

Keywords: Alzheimer’s disease; Amyloid beta; Long-term potentiation; Quadripulse stimulation; Synaptic plasticity; Tau; Transcranial magnetic stimulation.