Basal forebrain activity predicts functional degeneration in the entorhinal cortex and decreases with Alzheimer's Disease progression

Abstract

BACKGROUND AND OBJECTIVESRecent models of Alzheimers Disease (AD) suggest the nucleus basalis of Meynert (NbM) as the origin of structural degeneration followed by the entorhinal cortex (EC). However, the functional properties of NbM and EC regarding amyloid-{beta} and hyperphosphorylated tau remain unclear. METHODSWe analyzed resting-state (rs)fMRI data with CSF assays from the Alzheimers Disease Neuroimaging Initiative (ADNI, n=71) at baseline and two years later. RESULTSAt baseline, local activity, as quantified by fractional amplitude of low-frequency fluctuations (fALFF), 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. DISCUSSIONOur findings give novel insights into the pathogenesis of AD by showing that local activity in NbM is affected by proteinopathology and predicts functional degeneration within the EC.