Figure 1.

Proposed model of biomarker dynamics of hyperexcitability in humans. Amyloid load, measured by either cerebrospinal fluid (CSF) or Pittsburgh B compound amyloid ligand (PiB) positron emission tomography (PET), is the first to increase. Functional magnetic resonance imaging (fMRI) hippocampal activation is elevated in the preclinical and early prodromal Alzheimer’s disease (AD) phases, and subsequently decreases, with final hypoactivation in AD dementia stage. Tau load elevation, at CSF analysis or tau imaging, subsequently follows. Higher rates of MRI atrophy appear after fMRI hyperactivation and tau increase. Electroencephalogram (EEG) abnormalities increase longitudinally as disease progress, with suboptimal detection rates. The combined effect of Aβ amyloid and tau induces hyperexcitability in early and hypoexcitability in late disease stages, as depicted by fMRI hippocampal activation. Made in ©BioRender-biorender.com.