Using the Locus Coeruleus as a biomarker in Alzheimer's disease

Abstract

AbstractBackgroundNeuronal loss and tau aggregation in the Locus Coeruleus (LC) are suggested to be among the earliest pathologies in Alzheimer’s Disease (AD). However this remains to be investigated in vivo. Depletion of cortical noradrenaline (NA) concentration as a result of LC degeneration has proinflammatory effects on microglia and likely contributes to the neuroinflammatory changes observed in animal models of AD. However inflammatory changes within the human LC and the relation to inflammation seen in LC projection areas, e.g. the temporal cortex, has not been investigated.Method24 AD participants and 24 age and gender matched cognitively unimpaired subjects underwent a high resolution neuromelanin‐sensitive magnetic resonance imaging (NM‐MRI) scan to enable the LC to be visualised in vivo. A LC contrast ratio was generated by comparing maximum values in the anatomical location of the LC to a reference region in the adjacent pontine tegmentum. Additionally, immunohistochemistry is currently being performed to examine several inflammatory markers in the LC and temporal cortex of 60 human brains at varying stages of disease severity and in relation to the pathology.ResultIn the MRI study, the AD group had a lower LC‐CR compared to controls (p<0.05), which correlated with cognitive impairment. Inflammatory and neuropathological markers in the post‐mortem tissue are currently being quantified.ConclusionNM‐MRI may be useful as a biomarker for diagnosis in AD and suggests early degeneration of the LC. Tissue examination will characterise the inflammatory changes observed in patients in order to elucidate the pathological consequences of LC degeneration.