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Locus ceruleus degeneration is ubiquitous in Alzheimer's disease: possible implications for diagnosis and treatment.

Haglund, Mattias LU ; Sjöbeck, Martin LU and Englund, Elisabet LU orcid (2006) In Neuropathology 26(6). p.528-532
Abstract
Degeneration of the locus ceruleus (LC) and decreased cortical levels of norepinephrine are common findings in Alzheimer's disease (AD), but their significance is unknown. Because the noradrenergic system is accessible to pharmacological intervention, the role of LC degeneration and noradrenergic dysfunction in the pathogenesis and clinical manifestations of AD needs clarification. Hypothetically, loss of noradrenergic innervation could cause microvascular dysfunction and manifest as ischemia. The objectives of this study were to develop a scale for assessment of LC degeneration and to determine whether degeneration of the LC correlates quantitatively with either duration of clinical dementia, overall severity of AD pathology or with... (More)
Degeneration of the locus ceruleus (LC) and decreased cortical levels of norepinephrine are common findings in Alzheimer's disease (AD), but their significance is unknown. Because the noradrenergic system is accessible to pharmacological intervention, the role of LC degeneration and noradrenergic dysfunction in the pathogenesis and clinical manifestations of AD needs clarification. Hypothetically, loss of noradrenergic innervation could cause microvascular dysfunction and manifest as ischemia. The objectives of this study were to develop a scale for assessment of LC degeneration and to determine whether degeneration of the LC correlates quantitatively with either duration of clinical dementia, overall severity of AD pathology or with measures of ischemic non-focal white matter disease (WMD) in AD. This report is a pathological follow-up of a clinical longitudinal dementia study of 66 consecutive cases of AD without admixture of vascular dementia (VaD) from the Lund Longitudinal Dementia Study, neuropathologically diagnosed between 1990 and 1999. Ten cases of VaD were included for comparative purposes. No correlation between degree of LC degeneration and duration of dementia, AD or WMD severity was found. LC degeneration was significantly more severe in the AD group than in the VaD group. Even though LC degeneration was not associated with WMD or the severity of AD pathology in this AD material, we suggest that clinical studies on the consequences of noradrenergic dysfunction are warranted. Treatment augmenting noradrenergic signaling is available and safe. The marked difference in the level of LC degeneration between AD and VaD cases suggests that LC degeneration could be used as a diagnostic marker of AD. (Less)
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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
locus coeruleus, leukoaraiosis, neuropathology, vascular dementia
in
Neuropathology
volume
26
issue
6
pages
528 - 532
publisher
Wiley-Blackwell
external identifiers
  • wos:000243260700004
  • scopus:33751270153
ISSN
0919-6544
DOI
10.1111/j.1440-1789.2006.00725.x
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division IV (013230800), Division V (013230900), Pathology, (Lund) (013030000), Department of Psychogeriatrics (013304000)
id
022391b4-ae2d-43a3-a832-c8d56cb7d892 (old id 165151)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17203588&dopt=Abstract
date added to LUP
2016-04-01 12:25:21
date last changed
2021-02-17 08:08:18
@article{022391b4-ae2d-43a3-a832-c8d56cb7d892,
  abstract     = {Degeneration of the locus ceruleus (LC) and decreased cortical levels of norepinephrine are common findings in Alzheimer's disease (AD), but their significance is unknown. Because the noradrenergic system is accessible to pharmacological intervention, the role of LC degeneration and noradrenergic dysfunction in the pathogenesis and clinical manifestations of AD needs clarification. Hypothetically, loss of noradrenergic innervation could cause microvascular dysfunction and manifest as ischemia. The objectives of this study were to develop a scale for assessment of LC degeneration and to determine whether degeneration of the LC correlates quantitatively with either duration of clinical dementia, overall severity of AD pathology or with measures of ischemic non-focal white matter disease (WMD) in AD. This report is a pathological follow-up of a clinical longitudinal dementia study of 66 consecutive cases of AD without admixture of vascular dementia (VaD) from the Lund Longitudinal Dementia Study, neuropathologically diagnosed between 1990 and 1999. Ten cases of VaD were included for comparative purposes. No correlation between degree of LC degeneration and duration of dementia, AD or WMD severity was found. LC degeneration was significantly more severe in the AD group than in the VaD group. Even though LC degeneration was not associated with WMD or the severity of AD pathology in this AD material, we suggest that clinical studies on the consequences of noradrenergic dysfunction are warranted. Treatment augmenting noradrenergic signaling is available and safe. The marked difference in the level of LC degeneration between AD and VaD cases suggests that LC degeneration could be used as a diagnostic marker of AD.},
  author       = {Haglund, Mattias and Sjöbeck, Martin and Englund, Elisabet},
  issn         = {0919-6544},
  language     = {eng},
  number       = {6},
  pages        = {528--532},
  publisher    = {Wiley-Blackwell},
  series       = {Neuropathology},
  title        = {Locus ceruleus degeneration is ubiquitous in Alzheimer's disease: possible implications for diagnosis and treatment.},
  url          = {http://dx.doi.org/10.1111/j.1440-1789.2006.00725.x},
  doi          = {10.1111/j.1440-1789.2006.00725.x},
  volume       = {26},
  year         = {2006},
}