Synergistic association of Aβ and tau pathology with cortical neurophysiology and cognitive decline in asymptomatic older adults

Jonathan Gallego-Rudolf, Alex I. Wiesman, Alexa Pichet Binette, Sylvia Villeneuve, Sylvain Baillet, PREVENT-AD research group

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

Animal and computational models of Alzheimer’s disease (AD) indicate that early amyloid-β (Aβ) deposits drive neurons into a hyperactive regime, and that subsequent tau depositions manifest an opposite, suppressive effect as behavioral deficits emerge. Here we report analogous changes in macroscopic oscillatory neurophysiology in the human brain. We used positron emission tomography and task-free magnetoencephalography to test the effects of Aβ and tau deposition on cortical neurophysiology in 104 cognitively unimpaired older adults with a family history of sporadic AD. In these asymptomatic individuals, we found that Aβ depositions colocalize with accelerated neurophysiological activity. In those also presenting medial–temporal tau pathology, linear mixed effects of Aβ and tau depositions indicate a shift toward slower neurophysiological activity, which was also linked to cognitive decline. We conclude that early Aβ and tau depositions relate synergistically to human cortical neurophysiology and subsequent cognitive decline. Our findings provide insight into the multifaceted neurophysiological mechanisms engaged in the preclinical phases of AD.

Originalspråkengelska
Sidor (från-till)2130-2137
Antal sidor8
TidskriftNature Neuroscience
Volym27
Nummer11
DOI
StatusPublished - 2024 nov.

Ämnesklassifikation (UKÄ)

  • Neurovetenskaper

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