A case-control study of the locus coeruleus degeneration in Alzheimer's disease

Hou, Ruihua; Beardmore, Rebecca; Holmes, Clive; Osmond, Clive; Darekar, Angela

doi:10.1016/j.euroneuro.2020.12.013

Cited by 21 publications

(26 citation statements)

References 20 publications

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“…As LC cell loss is evident in AD brains, a reduction in LC signal in AD patients would be expected on NM-MRI, indeed volumetric reduction of the brainstem is observed in AD compared to cognitively normal individuals [182] To our knowledge, six in vivo studies using NM-MRI have studied the LC in AD. One reported no significant difference in LC signal intensity, though it employed a small sample size (n = 6) [180]; whereas four of the other studies showed a significant reduction in signal in AD patients [164,[183][184][185] when compared to healthy controls, which also correlated with an increase in CSF A␤ levels [185]. Additionally, LC signal was reported to be lower in those with MCI compared to controls [164], but this has not always been observed [185].…”

Section: Neuroimaging Nm/lc In Admentioning

confidence: 97%

“…However, postmortem studies have shown the LC to be bilaterally symmetrical [6-8, 11, 13] and the researchers employed a different method for calculating the LC contrast ratio (taking the maximum signal intensity values for each side and dividing by the left and right sides of the pons, respectively) as well as having a relatively small sample size. Only one of the studies used age and gender matched controls and excluded participants who were taking medications that may alter the noradrenergic system, e.g., serotonin and noradrenaline reuptake inhibitors [184]. Overall when LC signal is observed to be reduced in AD patients, it is the rostral and middle parts of the LC that are significantly different whereas the caudal section appears unchanged [185].…”

Section: Neuroimaging Nm/lc In Admentioning

confidence: 99%

“…Fig.3. NM-MR axial image of a 69 year old female with no cognitive impairment obtained on 3Tesla Siemens Skyra MRI scanner at the level approximately 7mm below the inferior colliculi, in which the LC can be observed as two hyperintense areas (red arrows)[184].…”

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confidence: 99%

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The Locus Coeruleus in Aging and Alzheimer’s Disease: A Postmortem and Brain Imaging Review

Beardmore

Hou

Darekar

et al. 2021

JAD

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The locus coeruleus (LC), a tiny nucleus in the brainstem and the principal site of noradrenaline synthesis, has a major role in regulating autonomic function, arousal, attention, and neuroinflammation. LC dysfunction has been linked to a range of disorders; however particular interest is given to the role it plays in Alzheimer’s disease (AD). The LC undergoes significant neuronal loss in AD, thought to occur early in the disease process. While neuronal loss in the LC has also been suggested to occur in aging, this relationship is less clear as the findings have been contradictory. LC density has been suggested to be indicative of cognitive reserve and the evidence for these claims will be discussed. Recent imaging techniques allowing visualization of the LC in vivo using neuromelanin-sensitive MRI are developing our understanding of the role of LC in aging and AD. Tau pathology within the LC is evident at an early age in most individuals; however, the relationship between tau accumulation and neuronal loss and why some individuals then develop AD is not understood. Neuromelanin pigment accumulates within LC cells with age and is proposed to be toxic and inflammatory when released into the extracellular environment. This review will explore our current knowledge of the LC changes in both aging and AD from postmortem, imaging, and experimental studies. We will discuss the reasons behind the susceptibility of the LC to neuronal loss, with a focus on the role of extracellular neuromelanin and neuroinflammation caused by the dysfunction of the LC-noradrenaline pathway.

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Section: Neuroimaging Nm/lc In Admentioning

confidence: 97%

Section: Neuroimaging Nm/lc In Admentioning

confidence: 99%

See 1 more Smart Citation

The Locus Coeruleus in Aging and Alzheimer’s Disease: A Postmortem and Brain Imaging Review

Beardmore

Hou

Darekar

et al. 2021

JAD

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“…The LC reveals degeneration and a loss of noradrenergic cells in alpha-synucleinopathies such as DLB (Iseki et al, 2001;Mori et al, 2002;Brunnström et al, 2011;Haglund et al, 2016, Table 1). The noradrenergic LC system often becomes degenerated early in both alpha-synucleinopathies such as Parkinson's disease (PD) (Solopchuk et al, 2018;Li et al, 2019), and ß-amyloidopathies like Alzheimer's disease (AD) (Zarow et al, 2003;Hou et al, 2021). Both diseases are closely related to Lewy body pathology, as mixed pathologies can coexist in patients with cognitive impairment (Coughlin et al, 2020).…”

Section: Degeneration Of the Locus Coeruleus In Dementia With Lewy Bomentioning

confidence: 99%

Locus Coeruleus Malfunction Is Linked to Psychopathology in Prodromal Dementia With Lewy Bodies

Hansen

2021

Front. Aging Neurosci.

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Background: The locus coeruleus (LC) is a nucleus in the human brainstem with a variety of noradrenaline-driven functions involved in cognition, emotions, and perception. Dementia with Lewy bodies (DLB) constitutes a neurodegenerative disease involving deposits of alpha-synuclein, first appearing in the brainstem. The goal of this narrative review is to delineate the relationship between the expression of psychiatric symptoms as an early-onset of DLB and the degeneration of the LC's noradrenaline system.Methods: We searched in PubMed for relevant articles concerning LC degeneration and psychiatric symptoms in prodromal DLB in this narrative review. We rely on the McKeith criteria for prodromal psychiatric DLB.Results: We found four studies that document neuronal loss, deposits of Lewy bodies and other hints for neurodegeneration in the LC in patients with DLB. Furthermore, we reviewed theories and studies on how the degenerated noradrenaline LC system contributes to psychiatric DLB's phenotype. We hypothesized how anxiety, hallucinations, delusions, and depressive symptoms might occur in DLB patients due to degenerated noradrenergic neurons entailing consecutive altered noradrenergic transmission in the LC's projection areas.Conclusions: LC degeneration in prodromal DLB might cause psychiatric symptoms as the first and non-motor manifestation of DLB, as the LC is affected earlier by degeneration than are dopaminergic structures such as the substantia nigra, which are impaired later in the disease course.

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“…Measuring pupil dilation could be an effective non-invasive way to monitor LC activity for early diagnosis ( Joshi et al, 2016 , Kremen et al, 2019 ). Alternatively, could be used traditional but more expensive magnetic resonance imaging approaches ( Betts et al, 2019 , Hou et al, 2021 , Liu et al, 2017 ). Another early diagnosis action could be monitoring 5-HT release through, for example, high-resolution PET imaging.…”

Section: Nes Hypothesis Supports Early Diagnosis and Advanced Therapi...mentioning

confidence: 99%

The Neurodegenerative Elderly Syndrome (NES) hypothesis: Alzheimer and Parkinson are two faces of the same disease

Caligiore

Giocondo

Silvetti

2022

IBRO Neuroscience Reports

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A case-control study of the locus coeruleus degeneration in Alzheimer's disease

Cited by 21 publications

References 20 publications

The Locus Coeruleus in Aging and Alzheimer’s Disease: A Postmortem and Brain Imaging Review

The Locus Coeruleus in Aging and Alzheimer’s Disease: A Postmortem and Brain Imaging Review

Locus Coeruleus Malfunction Is Linked to Psychopathology in Prodromal Dementia With Lewy Bodies

The Neurodegenerative Elderly Syndrome (NES) hypothesis: Alzheimer and Parkinson are two faces of the same disease

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