Early alteration of the locus coeruleus in phenotypic variants of Alzheimer’s disease

Abstract

Neuropathological studies showed early locus coeruleus (LC) neuronal loss associated with tauopathy in Alzheimer’s Disease (AD). We used the LC signal intensity (LC‐I) on 3T MRI to assess the LC integrity in AD (n = 37) and controls (n = 17). The LC‐I was decreased in AD regardless of typical (amnesic) and atypical presentation (logopenic aphasia/visuo‐spatial deficit), from the prodromal stage, and independently of the amyloid load measured by PiB‐PET. The LC‐I was correlated with memory performance of typical AD. This supports the pathophysiological model in which the LC plays a critical role in AD and may thus be a potential therapeutic target.

Correlation between cognition and plasma noradrenaline level in Alzheimer’s disease: a potential new blood marker of disease evolution

“…Most of the noradrenergic neurons in the CNS originate from the locus coeruleus (LC) and project to different areas of the brain, such as the cortex, hippocampus, amygdala, thalamus, and hypothalamus 10 . Hyperphosphorylation of Tau protein in the LC appears at an early stage of AD pathogenesis 11 , and the number of neurons in the LC has been shown to progressively decrease during the disease, beginning at the prodromal stage of AD 8,[12][13][14][15][16][17] . Based on the current literature, one of the ideas that has emerged is that the onset of AD is preceded by abnormal hyperactivation of the LC, resulting in oversecretion of NA in the cortex 18 .…”

What’s That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease

“…LC contrast is lower in AD and PD ( Figure 1E ) ( Sasaki et al, 2006 ; Takahashi et al, 2015 ; Dordevic et al, 2017 ; Wang et al, 2018 ; Betts et al, 2019a ; Olivieri et al, 2019 ). In AD, lower LC contrast is localized to the rostral and middle thirds of the nucleus ( Betts et al, 2019a ), which is in agreement with previous postmortem reports indicating patterned LC volume loss in AD but not PD ( German et al, 1992 ; Theofilas et al, 2017 ).…”

“…In healthy older adults, higher LC contrast is positively associated with cortical thickness ( Bachman et al, 2020 ), better memory performance ( Hämmerer et al, 2018 ; Dahl et al, 2019 ), and preserved cognition ( Liu et al, 2020 ). Early evidence suggests that even in subjects with typical AD presentation, high LC contrast is associated with better memory performance ( Olivieri et al, 2019 ). These studies are consistent with reports that postmortem LC integrity appears to encode neural reserve and cognitive function during healthy aging ( Robertson, 2013 ; Wilson et al, 2013 ), and LC contrast does correlate with known measures of neural reserve ( Clewett et al, 2016 ).…”

A probabilistic atlas of locus coeruleus pathways to transentorhinal cortex for connectome imaging in Alzheimer's disease

“…For the in vivo imaging of the LC, neuromelanin-sensitive MRI protocols were developed ( Keren et al, 2009 ; Priovoulos et al, 2018 ; Sasaki et al, 2006 ) and validated with histology ( Keren et al, 2015 ). These MRI protocols have been applied successfully in various studies to quantify the morphometry and signal intensity changes due to aging ( Betts et al, 2017 ; Clewett et al, 2015 ; Dahl et al, 2019 ; Liu et al, 2019 ) and AD ( Betts et al, 2019 ; Olivieri et al, 2019 ; Takahashi et al, 2015 ). In addition, resting state fMRI (rsfMRI) was applied recently to examine the functional connectivity of LC ( Jacobs et al, 2018b ; Zhang et al, 2015 ).…”