Differential degeneration of the locus coeruleus in dementia subtypes

Brunnström, Hans; Friberg, Niklas; Lindberg, Eva Hellström; Englund, Elisabet

doi:10.5414/npp30104

Cited by 51 publications

(50 citation statements)

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“…Despite the considerable role of the LC–norepinephrine system, the contribution of noradrenergic deficit (eg, TH metabolic deficits in the LC, the leading source of noradrenergic innervation in the brain) to cognitive dysfunction in PD, with some exceptions, is still underappreciated 24 61 83 168–172. Progress in the development of noradrenergic therapeutic interventions might not only alleviate depressive and/or anxiety symptoms42 44 but possibly also delay dementia onset 170.…”

Section: Discussionmentioning

confidence: 99%

Dysfunction of the locus coeruleus–norepinephrine system and related circuitry in Parkinson's disease-related dementia

Tredici

Braak

2012

J Neurol Neurosurg Psychiatry

217

160

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Although resting tremor, cogwheel rigidity, hypokinesia/bradykinesia and postural instability usually dominate the clinical picture of sporadic Parkinson's disease (PD), both clinical and epidemiological data reveal that a wide variety of additional symptoms impair patients’ quality of life considerably, parallel to the chronic progressive neurodegenerative movement disorder. Autopsy based retrospective studies have shown that α-synuclein immunoreactive Lewy pathology (LP) develops in the locus coeruleus (LC) of patients with neuropathologically confirmed sporadic PD, as well as in individuals with incidental (prodromal or premotor) Lewy body disease but not in age and gender matched controls. Using five case studies, this review discusses the possible role of LP (axonopathy, cellular dysfunction and nerve cell loss) in the LC, catecholaminergic tract and related circuitry in the development of PD-related dementia. The contribution of noradrenergic deficit to cognitive dysfunction in PD has been underappreciated. Noradrenergic therapeutic interventions might not only alleviate depressive symptoms and anxiety but also delay the onset of cognitive decline.

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Section: Discussionmentioning

confidence: 99%

Dysfunction of the locus coeruleus–norepinephrine system and related circuitry in Parkinson's disease-related dementia

Tredici

Braak

2012

J Neurol Neurosurg Psychiatry

217

160

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“…Indeed, as it has been demonstrated through multiple clinical reports, while each of these three pathologies have their unique pathological signatures, the disruption of sleep and circadian rhythms is one of the common and earliest signs of Alzheimer’s, Parkinson’s and Huntington’s diseases; abnormalities in the circadian clock and sleep worsen as the disease progresses 22, 82 (see details on neurodegeneration associated circadian disruption in Box1). Degeneration of brain nuclei containing sleep circuits and circadian clock-regulating circuits in the SCN 83, 84 , hypothalamus 85–87 , basal forebrain 85, 88 and brain stem 87, 89, 90 is one of the possible causes of sleep defects in patients with neurodegenerative diseases. These brain structures release different neurotransmitters; during wakefulness, excitatory neurotransmitters such as adrenaline, serotonin and histamine are released, whereas the release of inhibitory neurotransmitters such as GABA and galanin is suppressed.…”

Section: Neurodegenerative Diseases and The Circadian Clockmentioning

confidence: 99%

The circadian clock and pathology of the ageing brain

2012

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Ageing leads to functional deterioration of many brain systems, including the circadian clock - an internal time-keeping system that generates 24 hr rhythms in physiology and behaviour. Numerous clinical studies have established a direct correlation between the severity of neurodegenerative disorders, sleep disturbances and weakening of circadian clock functions. The latest data from model organisms, gene expression studies and clinical trials imply that the dysfunction of the circadian clock may contribute to the progression of ageing and age-associated pathologies, suggesting a functional link between the circadian clock, and age-associated decline of brain functions. Potential molecular mechanisms underlying this link include the circadian control of brain metabolism, reactive oxygen species homeostasis, hormone secretion, autophagy and stem cell proliferation.

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“…These results are promising and should be considered in future clinical treatment paradigms for DSD patients. Since LC-NE degeneration is common to both Parkinson's disease (PD) and AD patients [85–87], future pharmaceutical interventions for dementia may include enhancement of NE neurotransmission also for these neurological conditions. Promising clinical pilot studies have already been initiated in terms of the NE reuptake inhibitor Atomoxetine and memory loss in PD [88] and in Alzheimer's disease [89, 90] even though much remains to be done in terms of incorporating NE enhancement treatment for dementia.…”

Section: Locus Coeruleus Degeneration In Dsdmentioning

confidence: 99%

Age-Related Neurodegeneration and Memory Loss in Down Syndrome

Lockrow

Fortress

Granholm

2012

Current Gerontology and Geriatrics Research

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Down syndrome (DS) is a condition where a complete or segmental chromosome 21 trisomy causes variable intellectual disability, and progressive memory loss and neurodegeneration with age. Many research groups have examined development of the brain in DS individuals, but studies on age-related changes should also be considered, with the increased lifespan observed in DS. DS leads to pathological hallmarks of Alzheimer's disease (AD) by 40 or 50 years of age. Progressive age-related memory deficits occurring in both AD and in DS have been connected to degeneration of several neuronal populations, but mechanisms are not fully elucidated. Inflammation and oxidative stress are early events in DS pathology, and focusing on these pathways may lead to development of successful intervention strategies for AD associated with DS. Here we discuss recent findings and potential treatment avenues regarding development of AD neuropathology and memory loss in DS.

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Differential degeneration of the locus coeruleus in dementia subtypes

Cited by 51 publications

References 0 publications

Dysfunction of the locus coeruleus–norepinephrine system and related circuitry in Parkinson's disease-related dementia

Dysfunction of the locus coeruleus–norepinephrine system and related circuitry in Parkinson's disease-related dementia

The circadian clock and pathology of the ageing brain

Age-Related Neurodegeneration and Memory Loss in Down Syndrome

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