The VLPO analog in the human hypothalamus shows tau‐driven extreme loss of sleep‐regulating neurons in PSP and Alzheimer’s disease: unveiling the basis of NREM sleep dysfunction in tauopathies

In both AD and PSP, our research reveals substantial neuropathological changes in the IntN, with PSP exhibiting more pronounced alterations. These changes align with observed sleep dysfunction in both conditions. PSP features severe insomnia, although wake-promoting neurons remain relatively intact, thus a significant reduction in neurons controlling NREM-sleep could account for its clinical sleep disturbances. Conversely, AD displays a decline in wake-promoting neurons and a gradual, moderate loss of NREM neurons, both leading to excessive daytime sleepiness and sleep fragmentation, yet overall preserved total sleep time. These findings deepen our understanding of NREM sleep dysfunction in tauopathies, offering insights for targeted interventions.