Locus coeruleus (LC) neurodegeneration is associated with cognitive deterioration during the transition from normal cognition to mild cognitive impairment (MCI) and Alzheimer disease (AD). However, the extent to which LC degenerative processes differentiate cognitively normal, "resilient" subjects bearing a high AD pathological burden from those with MCI or AD remains unclear. We approached this problem by quantifying the number of LC neurons and the percentage of LC neurons bearing AT8 tau pathology, TDP- 43 pathology, or a marker for DNA/RNA oxidative damage, in wellcharacterized subjects diagnosed as normal cognition-low AD pathology (NC-LP), NC-high AD pathology (NC-HP), MCI, or mild/ moderate AD. In addition, the severity of pontine arteriolosclerosis in each subject was compared across the groups. There was a trend for a step-wise _20% loss of LC neuron number between the NCLP, NC-HP and MCI subjects despite a successive, significant _80%-100% increase in tau pathology between these groups. In contrast, increasing pontine arteriolosclerosis severity scores and LC oxidative stress burden significantly separated the NC-LP/HP and MCI/AD groups via comparative, correlation, and regression analysis. Pontine perfusion, as well as LC neuronal metabolic and redox function, may impact noradrenergic LC modulation of cognition during the preclinical and prodromal stages of AD. VC 2021 American Association of Neuropathologists, Inc.
|Number of pages||11|
|Journal||Journal of Neuropathology and Experimental Neurology|
|State||Published - Apr 1 2021|
Bibliographical noteFunding Information:
This study was supported by NIH R01 AG060731, P01 AG014449, P30 AG053760, and P30 AG028383, as well as donors to the BrightFocus Foundation (ADR20201187S), the Saint Mary’s Foundation, and Miles for Memories of Battle Creek, MI.
© 2021 Oxford University Press. All rights reserved.
- Alzheimer disease
- Locus coeruleus
- Mild cognitive impairment
- Oxidative stress
ASJC Scopus subject areas
- Medicine (all)