학술논문

Spatiotemporal characteristics of neurophysiological changes in patients with four‐repeat tauopathies
Document Type
article
Source
Annals of Clinical and Translational Neurology. 11(2)
Subject
Biological Psychology
Biomedical and Clinical Sciences
Psychology
Acquired Cognitive Impairment
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Rare Diseases
Brain Disorders
Pick's Disease
Neurodegenerative
Dementia
Neurosciences
Alzheimer's Disease
Frontotemporal Dementia (FTD)
Aging
Alzheimer's Disease Related Dementias (ADRD)
2.1 Biological and endogenous factors
Neurological
Humans
tau Proteins
Tauopathies
Alzheimer Disease
Supranuclear Palsy
Progressive
Brain
Clinical Sciences
Clinical and health psychology
Language
Abstract
IntroductionProgressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are the most common four-repeat tauopathies (4RT), and both frequently occur with varying degree of Alzheimer's disease (AD) copathology. Intriguingly, patients with 4RT and patients with AD are at opposite ends of the wakefulness spectrum-AD 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-state in the human brain, in patients with primary 4RT, and how it is modified in comorbid AD-pathology.MethodIn an autopsy-confirmed case series of 4R-tauopathy patients (n = 10), whose primary neuropathological diagnosis was either PSP (n = 7) or CBD (n = 3), using high spatiotemporal resolution magnetoencephalography (MEG), we quantified the spectral power density within alpha-band (8-12 Hz) and examined how this pattern was modified in increasing AD-copathology. For each patient, their regional alpha power was compared to an age-matched normative control cohort (n = 35).ResultPatients with 4RT showed increased alpha power but in the presence of AD-copathology alpha power was reduced.ConclusionsAlpha power increase in PSP-tauopathy and reduction in the presence of AD-tauopathy is consistent with the observation that neurons activating wakefulness-promoting systems are preserved in PSP but degenerated in AD. These results highlight the selectively vulnerable impacts in 4RT versus AD-tauopathy that may have translational significance on disease-modifying therapies for specific proteinopathies.