P4‐074: Early Detection of Abnormal Sensory‐evoked Eeg Responses in Mice Over‐expressing Amyloid Beta
Year: 2019
Type: article
Abstract: The disruptive effects of β-amyloid (Aβ) on synaptic function have been well established and there are therapies currently in development targeting Aβ pathology in Alzheimer's patients. However, it has been proposed that early intervention reducing Aβ burden would have the most beneficial outcome for halting or reversing disease progression. In the present studies, we investigated neuronal circuit integrity in sensory processing in Aβ overexpressing transgenic mice at young ages and explored test-retest reliability of these measures in humans. Neurophysiological recordings were performed bilaterally from the surface of the dura over frontal, parietal and visual cortex in Tg2576, Aβ overproducing transgenic mice and age-matching wild type (WT) mice monthly, beginning at 3 months of age. For human EEG, recordings from young healthy volunteers were acquired using a 128-channel BioSemi ActiveTwo system. For Steady State Visually Evoked Responses (SSVEPs) light pulses were presented at a rate of 15 and 40Hz. The duration of the stimuli were 3 seconds, repeated every 20 seconds. The SSVEP was found to contain both stimulus-locked (evoked) and stimulus associated (induced) components in both humans and mice. Evoked responses contained typical oscillations that included transient visually evoked potentials (VEPs) and the steady state portion showing frequency congruent with the fundamental frequency of the stimulus. Tg2576 mice displayed consistently larger VEP amplitudes, and significantly altered stimulus-associated, induced gamma and beta oscillations compared to WT controls. Tg2576 mice also showed an increased EEG power at baseline. Human EEG recordings, taken from an identical assay, produced robust on/off VEPs as well as SSVEPs consistent with literature findings with the addition of significant suppression of ongoing alpha (∼10 Hz) that emerged during the dark, inter-trial intervals. Tg2576 mice show altered “induced” responses to flickering visual stimuli, elevated VEP amplitudes and increased broadband EEG power at ages when little or no insoluble Amyloid plaques can be detected. Our finding suggest that the EEG based SSVEP may be useful as a biomarker in identifying patients with early amyloid pathology and/or cognitive decline.
Source: Alzheimer s & Dementia
Authors: Brian D. Harvey, Robert Komorowski, Rocco Palumbo, Kevin M. Spencer, Andrew Budson, Mihaly Hajos
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2981150185