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Intriguingly, patients with 4RT and patients with AD are at opposite ends of the wakefulness spectrum\u2014AD showing reduced wakefulness and excessive sleepiness whereas 4RT showing decreased homeostatic sleep. The neural mechanisms underlying these distinct phenotypes in the comorbid condition of 4RT and AD are unknown. The objective of the current study was to define the alpha oscillatory spectrum, which is prominent in the awake resting\u2010state in the human brain, in patients with primary 4RT, and how it is modified in comorbid AD\u2010pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>In an autopsy\u2010confirmed case series of 4R\u2010tauopathy patients (<jats:italic>n<\/jats:italic>\u2009=\u200910), whose primary neuropathological diagnosis was either PSP (<jats:italic>n<\/jats:italic>\u2009=\u20097) or CBD (<jats:italic>n<\/jats:italic>\u2009=\u20093), using high spatiotemporal resolution magnetoencephalography (MEG), we quantified the spectral power density within alpha\u2010band (8\u201312\u2009Hz) and examined how this pattern was modified in increasing AD\u2010copathology. For each patient, their regional alpha power was compared to an age\u2010matched normative control cohort (<jats:italic>n<\/jats:italic>\u2009=\u200935).<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>Patients with 4RT showed increased alpha power but in the presence of AD\u2010copathology alpha power was reduced.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Alpha power increase in PSP\u2010tauopathy and reduction in the presence of AD\u2010tauopathy is consistent with the observation that neurons activating wakefulness\u2010promoting systems are preserved in PSP but degenerated in AD. These results highlight the selectively vulnerable impacts in 4RT versus AD\u2010tauopathy that may have translational significance on disease\u2010modifying therapies for specific proteinopathies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51974","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T14:15:31Z","timestamp":1705414531000},"page":"525-535","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Spatiotemporal characteristics of neurophysiological changes in patients with four\u2010repeat tauopathies"],"prefix":"10.1002","volume":"11","author":[{"given":"Niyatee","family":"Samudra","sequence":"first","affiliation":[{"name":"Memory and Aging Center, Department of Neurology Weill Institute for Neurosciences, University of California San Francisco  San Francisco California 94158 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