Increasing pontine arteriolosclerosis and LC oxidative stress significantly separated cognitively normal subjects from MCI/AD, despite a ~80%-100% increase in tau pathology between groups.
Cohort
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 well-characterized 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 NC-LP, 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.
Kelly et al. (Mon,) conducted a cohort in Mild Cognitive Impairment and Alzheimer Disease. Pontine arteriolosclerosis and locus coeruleus oxidative stress vs. Normal cognition (NC-LP/HP) was evaluated on Differentiation of NC-LP/HP and MCI/AD groups. Increasing pontine arteriolosclerosis and LC oxidative stress significantly separated cognitively normal subjects from MCI/AD, despite a ~80%-100% increase in tau pathology between groups.