Neurobehavioral and Neuropsychiatric Symptoms in Alzheimer's Disease

Chung, Julia; Cummings, Jeffrey L.

doi:10.1016/s0733-8619(05)70228-0

Cited by 154 publications

(110 citation statements)

References 82 publications

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“…hAPP mice with reduced Sod2 exhibited less anxiety-like behavior (or more disinhibition) in the plus maze, consistent with recently identified correlations between anxiety-like behavior and antioxidant levels (Hovatta et al, 2005;Krömer et al, 2005). Although the exact relationship between these alterations in mice and AD in humans is tentative, AD patients clearly have altered emotional behaviors and activity levels (Chung and Cummings, 2000;Harper et al, 2004;Hatfield et al, 2004).…”

Section: Discussionsupporting

confidence: 84%

Reduction in Mitochondrial Superoxide Dismutase Modulates Alzheimer's Disease-Like Pathology and Accelerates the Onset of Behavioral Changes in Human Amyloid Precursor Protein Transgenic Mice

Esposito¹,

Raber²,

Kekonius³

et al. 2006

J. Neurosci.

233

166

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Alzheimer's disease (AD) is associated with accumulations of amyloid-␤ (A␤) peptides, oxidative damage, mitochondrial dysfunction, neurodegeneration, and dementia. The mitochondrial antioxidant manganese superoxide dismutase-2 (Sod2) might protect against these alterations. To test this hypothesis, we inactivated one Sod2 allele (Sod2 ϩ/Ϫ ) in human amyloid precursor protein (hAPP) transgenic mice, reducing Sod2 activity to ϳ50% of that in Sod2 wild-type (Sod2 ϩ/ϩ ) mice. A reduction in Sod2 activity did not obviously impair mice without hAPP/A␤ expression. In hAPP mice, however, it accelerated the onset of behavioral alterations and of deficits in prepulse inhibition of acoustic startle, a measure of sensorimotor gating. In these mice, it also worsened hAPP/A␤-dependent depletion of microtubule-associated protein 2, a marker of neuronal dendrites. Sod2 reduction decreased amyloid plaques in the brain parenchyma but promoted the development of cerebrovascular amyloidosis, gliosis, and plaque-independent neuritic dystrophy. Sod2 reduction also increased the DNA binding activity of the transcription factor nuclear factor B. These results suggest that Sod2 protects the aging brain against hAPP/A␤-induced impairments. Whereas reductions in Sod2 would be expected to trigger or exacerbate neuronal and vascular pathology in AD, increasing Sod2 activity might be of therapeutic benefit.

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Section: Discussionsupporting

confidence: 84%

Reduction in Mitochondrial Superoxide Dismutase Modulates Alzheimer's Disease-Like Pathology and Accelerates the Onset of Behavioral Changes in Human Amyloid Precursor Protein Transgenic Mice

Esposito¹,

Raber²,

Kekonius³

et al. 2006

J. Neurosci.

233

166

View full text Add to dashboard Cite

show abstract

“…Questions such as how this prior occurrence of biochemical and histological changes specifically affects the process of neuronal loss, which factors in the aging brain critically lead to neuronal loss and behavioral impairments, what the neuronal properties of the degenerating neurons are, and what strategy is needed to delay or protect the pathophysiology of the AD-like brain can potentially be answered using this Tg-hCTF99/B6 model. Fifth, Tg-hCTF99/B6 mice showed increased anxiety and cognitive impairments, which are the behavioral features observed in the human AD brain (Chemerinski et al, 1998;Folstein and Bylsma, 1999;Chung and Cummings, 2000;Ownby et al, 2000). Above all, the fact that these phenotypes are presented by a single transgenic line is intriguing.…”

Section: Neuropathological Features Of Tg-bctf99/b6 As An Ad Modelmentioning

confidence: 96%

“…The increased anxiety shown by Tg-bCTF99/B6 mice Increased anxiety is a problematic symptom of human AD (Chemerinski et al, 1998;Folstein and Bylsma, 1999;Chung and Cummings, 2000;Ownby et al, 2000). Histological deterioration and various biochemical alterations in the brain led us to examine the anxiety-related behaviors of Tg-hCTF99/B6 mice.…”

Section: Impaired Cognitive Function Of Tg-bctf99/b6mentioning

confidence: 99%

Progressive neuronal loss and behavioral impairments of transgenic C57BL/6 inbred mice expressing the carboxy terminus of amyloid precursor protein

Lee

Song

et al. 2006

Neurobiology of Disease

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“…Neuropsychiatric symptoms are associated with a rapid course of decline, elevated caregiver distress, and increased utilization of healthcare services [3,4]. Apathy is the most common neuropsychiatric symptom reported among individuals with AD, affecting approximately 70% of patients in the mild-moderate stages [2,5] and over 90% of patients in the later stages [6].…”

Section: Introductionmentioning

confidence: 99%

Treating Apathy in Alzheimer’s Disease

Boyle

Malloy²

2003

Dement Geriatr Cogn Disord

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Apathy, a syndrome of decreased initiation and motivation, affects over 70% of individuals with Alzheimer’s disease (AD) and is the most common neuropsychiatric symptom reported in AD patients. The syndrome of apathy is associated with functional impairment among patients and elevated stress among their caregivers. Apathy is one of the primary neuropsychiatric manifestations of frontal system dysfunction, and AD-related apathy is thought to reflect the interaction between cholinergic deficiency and neuropathological changes in frontal brain regions. This article reviews the assessment and treatment of apathy in AD, with emphasis on the utility of acetylcholinesterase inhibitors for reducing apathy in AD. The potential benefits of other pharmacologic agents and combined pharmacologic-behavioral interventions are also discussed, and recommendations for future research are provided.

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Neurobehavioral and Neuropsychiatric Symptoms in Alzheimer's Disease

Cited by 154 publications

References 82 publications

Reduction in Mitochondrial Superoxide Dismutase Modulates Alzheimer's Disease-Like Pathology and Accelerates the Onset of Behavioral Changes in Human Amyloid Precursor Protein Transgenic Mice

Reduction in Mitochondrial Superoxide Dismutase Modulates Alzheimer's Disease-Like Pathology and Accelerates the Onset of Behavioral Changes in Human Amyloid Precursor Protein Transgenic Mice

Progressive neuronal loss and behavioral impairments of transgenic C57BL/6 inbred mice expressing the carboxy terminus of amyloid precursor protein

Treating Apathy in Alzheimer’s Disease

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