title: Interictal spikes during sleep are an early defect in the Tg2576 mouse model of β-amyloid neuropathology.
abstract: It has been suggested that neuronal hyperexcitability contributes to Alzheimer's disease (AD), so we asked how hyperexcitability develops in a common mouse model of β-amyloid neuropathology - Tg2576 mice. Using video-EEG recordings, we found synchronized, large amplitude potentials resembling interictal spikes (IIS) in epilepsy at just 5 weeks of age, long before memory impairments or β-amyloid deposition. Seizures were not detected, but they did occur later in life, suggesting that IIS are possibly the earliest stage of hyperexcitability. Interestingly, IIS primarily occurred during rapid-eye movement (REM) sleep, which is notable because REM is associated with increased cholinergic tone and cholinergic impairments are implicated in AD. Although previous studies suggest that cholinergic antagonists would worsen pathophysiology, the muscarinic antagonist atropine reduced IIS frequency. In addition, we found IIS occurred in APP51 mice which overexpress wild type (WT)-APP, although not as uniformly or as early in life as Tg2576 mice. Taken together with results from prior studies, the data suggest that surprising and multiple mechanisms contribute to hyperexcitability. The data also suggest that IIS may be a biomarker for early detection of AD.
authors.affiliation: The Nathan Kline Institute for Psychiatric Research Center for Dementia Research Orangeburg, NY 10962, USA.|Graduate Program in Physiology and Neuroscience New York University Langone Medical Center New York, NY 10016, USA.
authors.forename: Korey
authors.initials: K
authors.lastname: Kam
authors.affiliation: The Nathan Kline Institute for Psychiatric Research Center for Dementia Research Orangeburg, NY 10962, USA.|Department of Physiology and Neuroscience New York University Langone Medical Center New York, NY 10016, USA.
authors.forename: Áine M
authors.initials: ÁM
authors.lastname: Duffy
authors.affiliation: The Nathan Kline Institute for Psychiatric Research Center for Dementia Research Orangeburg, NY 10962, USA.
authors.forename: Jillian
authors.initials: J
authors.lastname: Moretto
authors.affiliation: The Nathan Kline Institute for Psychiatric Research Center for Dementia Research Orangeburg, NY 10962, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: LaFrancois
authors.affiliation: The Nathan Kline Institute for Psychiatric Research Center for Dementia Research Orangeburg, NY 10962, USA.|Department of Physiology and Neuroscience New York University Langone Medical Center New York, NY 10016, USA.|Department of Child and Adolescent Psychiatry and Psychiatry New York University Langone Medical Center New York, NY 10016, USA.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Scharfman
mesh_terms: D000200:Action Potentials; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D058256:Brain Waves; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D004569:Electroencephalography; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D012890:Sleep; D012895:Sleep, REM
chemical_list: D016229:Amyloid beta-Peptides; D016760:Proto-Oncogene Proteins c-fos; D011976:Receptors, Muscarinic; D002795:Choline O-Acetyltransferase
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