Degeneration in Nucleus basalis of Meynert signals earliest stage of Alzheimer's disease progression

Neurobiol Aging. 2024 Jul:139:54-63. doi: 10.1016/j.neurobiolaging.2024.03.003. Epub 2024 Mar 15.


Nucleus Basalis of Meynert (NbM), a crucial source of cholinergic projection to the entorhinal cortex (EC) and hippocampus (HC), has shown sensitivity to neurofibrillary degeneration in the early stages of Alzheimer's Disease. Using deformation-based morphometry (DBM) on up-sampled MRI scans from 1447 Alzheimer's Disease Neuroimaging Initiative participants, we aimed to quantify NbM degeneration along the disease trajectory. Results from cross-sectional analysis revealed significant differences of NbM volume between cognitively normal and early mild cognitive impairment cohorts, confirming recent studies suggesting that NbM degeneration happens before degeneration in the EC or HC. Longitudinal linear mixed-effect models were then used to compare trajectories of volume change after realigning all participants into a common timeline based on their cognitive decline. Results indicated the earliest deviations in NbM volumes from the cognitively healthy trajectory, challenging the prevailing idea that Alzheimer's originates in the EC. Converging evidence from cross-sectional and longitudinal models suggest that the NbM may be a focal target of early AD progression, which is often obscured by normal age-related decline.

Keywords: Alzheimer’s disease; Basal Forebrain; Deformation-based morphometry; Entorhinal Cortex; Hippocampus; Nucleus Basalis of Meynert; Super-resolution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / pathology
  • Basal Nucleus of Meynert* / diagnostic imaging
  • Basal Nucleus of Meynert* / pathology
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / pathology
  • Cross-Sectional Studies
  • Disease Progression*
  • Entorhinal Cortex / diagnostic imaging
  • Entorhinal Cortex / pathology
  • Female
  • Hippocampus / diagnostic imaging
  • Hippocampus / pathology
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging*
  • Male
  • Organ Size