P50: A candidate ERP biomarker of prodromal Alzheimer's disease

Abstract

Introduction: Reductions of cerebrospinal fluid (CSF) amyloid-beta (Aβ42) and elevated phosphorylated-tau (p-Tau) reflect in vivo Alzheimer's disease (AD) pathology and show utility in predicting conversion from mild cognitive impairment (MCI) to dementia. We investigated the P50 event-related potential component as a noninvasive biomarker of AD pathology in non-demented elderly.

Methods: 36 MCI patients were stratified into amyloid positive (MCI-AD, n=17) and negative (MCI-Other, n=19) groups using CSF levels of Aβ42. All amyloid positive patients were also p-Tau positive. P50s were elicited with an auditory oddball paradigm.

Results: MCI-AD patients yielded larger P50s than MCI-Other. The best amyloid-status predictor model showed 94.7% sensitivity, 94.1% specificity and 94.4% total accuracy.

Discussion: P50 predicted amyloid status in MCI patients, thereby showing a relationship with AD pathology versus MCI from another etiology. The P50 may have clinical utility for inexpensive pre-screening and assessment of Alzheimer's pathology.

Keywords: Alzheimer׳s disease (AD); Amyloid-beta; Auditory oddball paradigm; Cerebrospinal fluid biomarkers; Event-related potential (ERP); P50.

Published by Elsevier B.V.

Figures

Fig. 1

ERP Grand average waveforms at frontal (Fz), central (Cz) and parietal (Pz) midline electrodes in response to standard, target, and novel stimuli. Time goes from left to right on the horizontal axis. Negative voltages are plotted up on the vertical axis according to convention. ERPs were computed with a 200 ms baseline prior to stimulus onset (at 0 ms). A 25-Hz lowpass filter was applied prior to individual ERP computation. The P50 component is indicated in the standard ERP at electrode Cz. The N1, P2, and P3 components are indicated in the novel ERP at electrode Cz.

Fig. 2

Frequency distributions of P50 amplitudes at electrode Cz, showing the percentage of participants with values within each .5 μV bin (left). Regression lines overlay scatterplots of P50 amplitudes at electrode Cz and CSF Aβ42 for all stimuli (right).

Fig. 3

Frequency distribution of P50 amplitude at electrode C3, showing the percentage of participants with values within each .5 μV bin (top). Partial correlation controlling for education revealed a significant negative relationship between Aβ42 and standard P50 amplitude at C3, r = −.49, p = .003 (middle). P50 and years education as predictors of Aβ42 (bottom).