Article
Neuron loss in key cholinergic and aminergic nuclei in Alzheimer disease: a meta-analysis.
Department of Neurology, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
Neurobiology of Aging (impact factor:
6.19).
24(1):1-23.
pp.1-23
Source: PubMed
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Citations (0)
- Cited In (13)
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Article: β-Adrenergic Receptors and G Protein-Coupled Receptor Kinase-2 in Alzheimer's Disease: A New Paradigm for Prognosis and Therapy?
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ABSTRACT: Alzheimer's disease (AD) is a devastating form of dementia that imposes a severe burden on health systems and society. Although several aspects of AD pathogenesis have been elucidated over the last few decades, many questions still need to be addressed. In fact, currently available medications only provide symptomatic improvement in patients with AD without affecting disease progression. The β-adrenergic receptor (β-AR) system can be considered a possible target that deserves further exploration in AD. The central noradrenergic system undergoes substantial changes in the course of AD and β-ARs have been implicated not only in amyloid formation in AD brain but also in amyloid-induced neurotoxicity. Moreover, clinical evidence suggests a protective role of β-AR blockers on AD onset. In addition to that, post-receptor components of β-AR signaling seem to have a role in AD pathogenesis. In particular, the G protein coupled receptor kinase 2, responsible for β-AR desensitization and downregulation, mediates amyloid-induced β-AR dysfunction in neurons, and its levels in circulating lymphocytes of AD patients are increased and inversely correlated with patient's cognitive status. Therefore, there is an urgent need to gain further insight on the role of the adrenergic system components in AD pathogenesis in order to translate preclinical and clinical knowledge to more efficacious prognostic and therapeutic strategies.Journal of Alzheimer's disease: JAD 12/2012; · 3.74 Impact Factor -
Article: The Association of Neuropsychiatric Symptoms in MCI With Incident Dementia and Alzheimer Disease.
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ABSTRACT: OBJECTIVES:: Individuals with mild cognitive impairment (MCI) are at high risk of developing dementia and/or Alzheimer disease (AD). Among persons with MCI, depression and anxiety have been associated with an increased risk of incident dementia. We examined whether neuropsychiatric symptoms in MCI increased the risk of incident dementia (all-cause) and incident AD. DESIGN:: Longitudinal cohort study followed annually (median: 1.58 years). SETTING:: National Alzheimer's Coordinating Center database combining clinical data from 29 Alzheimer's Disease Centers. PARTICIPANTS:: A total of 1,821 participants with MCI. MEASUREMENTS:: 1) Progression to dementia (all-cause) or AD, 2) Neuropsychiatric Inventory Questionnaire (NPI-Q), 3) Geriatric Depression Scale (GDS), 4) Clinical Dementia Rating Global Score and Sum of Boxes, and 5) Mini-Mental State Examination(MMSE). The association of covariates with risk of incident dementia or AD was evaluated with hazard ratios (HR) determined by Cox proportional-hazards models adjusted for age, ethnicity, Clinical Dementia Rating Global Score and Sum of Boxes, and MMSE. RESULTS:: A total of 527 participants (28.9%) progressed to dementia and 454 (24.9%) to AD. Baseline GDS > 0 was associated with an increased risk of incident dementia (HR: 1.47, 95% CI: 1.17-1.84) and AD (HR: 1.45, 95% CI: 1.14-1.83). Baseline NPI > 0 was associated with an increased risk of incident dementia (HR: 1.37, 95% CI: 1.12-1.66) and AD (HR: 1.35, 95% CI: 1.09-1.66). CONCLUSIONS:: Neuropsychiatric symptoms in MCI are associated with significantly an increased risk of incident dementia and AD. Neuropsychiatric symptoms may be among the earliest symptoms of preclinical stages of AD and targeting them therapeutically might delay transition to dementia.The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 04/2012; · 3.35 Impact Factor -
Article: Locus coeruleus damage and noradrenaline reductions in multiple sclerosis and experimental autoimmune encephalomyelitis.
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ABSTRACT: The endogenous neurotransmitter noradrenaline exerts anti-inflammatory and neuroprotective effects in vitro and in vivo. Several studies report that noradrenaline levels are altered in the central nervous system of patients with multiple sclerosis and rodents with experimental autoimmune encephalomyelitis, which could contribute to pathology. Since the major source of noradrenaline are neurons in the locus coeruleus, we hypothesized that alterations in noradrenaline levels are a consequence of stress or damage to locus coeruleus neurons. In C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein peptide 35-55 to develop chronic disease, cortical and spinal cord levels of noradrenaline were significantly reduced versus control mice. Immunohistochemical staining revealed increased astrocyte activation in the ventral portion of the locus coeruleus in immunized mice. The immunized mice showed neuronal damage in the locus coeruleus detected by a reduction of average cell size of tyrosine hydroxylase stained neurons. Analysis of the locus coeruleus of multiple sclerosis and control brains showed a significant increase in astrocyte activation, a reduction in noradrenaline levels, and neuronal stress indicated by hypertrophy of tyrosine hydroxylase stained cell bodies. However, the magnitude of these changes was not correlated with extent of demyelination or of cellular infiltrates. Together these findings demonstrate the presence of inflammation and neuronal stress in multiple sclerosis as well as in experimental autoimmune encephalomyelitis. Since reduced noradrenaline levels could be permissive for increased inflammation and neuronal damage, these results suggest that methods to raise noradrenaline levels or increase locus coeruleus function may be of benefit in treating multiple sclerosis.Brain 02/2011; 134(Pt 3):665-77. · 9.46 Impact Factor
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Keywords
11 studies
14 studies
24 studies
33 studies
ameliorating multiple neurotransmitter deficiencies
Cell counts
cell loss
cholinergic nucleus basalis
dopaminergic substantia nigra
effect size estimates
effect size magnitude
Effect sizes
four cell areas
noradrenergic
noradrenergic locus coeruleus
primary-level reports
serotonergic dorsal raphe nucleus
smallest
Symptomatic drug treatment
times greater
