Alzheimer’s disease (AD) is the most common form of dementia, progressively impairing memory
and cognition. While neuroimaging studies have revealed functional abnormalities in AD, how these
relate to aberrant neuronal circuit mechanisms remains unclear. We employed a spectral graph-theory
model (SGM) to identify abnormal biophysical markers of neuronal activity in AD. SGM is an analytic
model that describes how long-range fiber projections in the brain mediate excitatory and inhibitory
activity of local neuronal subpopulations. We estimated SGM parameters that captured the regional power
spectra obtained from magnetoencephalography imaging of a well-characterized population of patients
with AD and controls. The long-range excitatory time constant was the most important feature for the
accurate classification of AD and controls and was associated with global cognitive deficits in AD. These
results indicate that a global impairment in the long-range excitatory neurons might be a sufficient factor
underlying spatiotemporal alterations of neuronal activity in AD.