Basal Forebrain Activity Predicts Functional Degeneration in the Entorhinal Cortex in Alzheimer’s Disease

Abstract Recent models of Alzheimer’s disease suggest the nucleus basalis of Meynert (NbM) as an early origin of structural degeneration followed by the entorhinal cortex (EC). However, the functional properties of NbM and EC regarding amyloid-β and hyperphosphorylated tau remain unclear. We analysed resting-state functional fMRI data with CSF assays from the Alzheimer’s Disease Neuroimaging Initiative (n = 71) at baseline and 2 years later. At baseline, local activity, as quantified by fractional amplitude of low-frequency fluctuations, differentiated between normal and abnormal CSF groups in the NbM but not EC. Further, NbM activity linearly decreased as a function of CSF ratio, resembling the disease status. Finally, NbM activity predicted the annual percentage signal change in EC, but not the reverse, independent from CSF ratio. Our findings give novel insights into the pathogenesis of Alzheimer’s disease by showing that local activity in NbM is affected by proteinopathology and predicts functional degeneration within the EC.