β-Amyloid accumulation in aged canine brain: A model of early plaque formation in Alzheimer's disease

Cummings, Brian J.; Su, Jianping; Cotman, Carl W.; White, R. G.; Russell, Michael J.

doi:10.1016/0197-4580(93)90038-d

Cited by 184 publications

(90 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the aging canine, no significant correlation between the levels of Aβ deposition in brain and oxidative damage is observed [54], however, since the aging canine deposits the more toxic form of Aβ 1-42 as that seen in human aging [19,74] and since Aβ load and decline in cognitive function events develop in parallel, Aβ could still play a significant role in the mechanism of oxidative stress observed in the aging canine [42,43,52]. In the peptide sequence of Aβ (1-42), there is a methionine-35 residue that our laboratory has shown to play a critical role in Aβ induced oxidative stress and neurotoxicity observed in AD [24].…”

Section: Discussionmentioning

confidence: 99%

Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: Relevance to Alzheimer's disease

Opii

Joshi

Head

et al. 2008

Neurobiology of Aging

Self Cite

175

135

View full text Add to dashboard Cite

Aging and age-related disorders such as Alzheimer's disease (AD) are usually accompanied by oxidative stress as one of the main mechanisms contributing to neurodegeneration and cognitive decline. Aging canines develop cognitive dysfunction and neuropathology similar to those seen in humans, and the use of antioxidants results in reductions in oxidative damage and in improvement in cognitive function in this canine model of human aging. In the present study, the effect of a longterm treatment with an antioxidant fortified diet and a program of behavioral enrichment on oxidative damage was studied in aged canines. To identify the neurobiological mechanisms underlying these treatment effects, the parietal cortex from 23 beagle dogs (8.1-12.4 years) were treated for 2.8 years in one of four treatment groups: i.e., control food-control behavioral enrichment (CC); control food -behavioral enrichment (CE); antioxidant food-control behavioral enrichment (CA); and enriched environment -antioxidant fortified food (EA). We analyzed the levels of the oxidative stress biomarkers, i.e., protein carbonyls, 3-nitrotyroine (3NT), and the lipid peroxidation product, 4- Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeurobiol Aging. Author manuscript; available in PMC 2009 January 1. Published in final edited form as:Neurobiol Aging. 2008 January ; 29(1): 51-70. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript hydroxynonenal (HNE), and observed a decrease in their levels on all treatments when compared to control, with the most significant effects found in the combined treatment, EA. Since EA treatment was most effective, we also carried out a comparative proteomics study to identify specific brain proteins that were differentially expressed and used a parallel redox proteomics approach to identify specific brain proteins that were less oxidized following EA. The specific protein carbonyl levels of glutamate dehydrogenase [NAD (P)], glyceraldehyde-3-phosphate dehydrogenase (GAPDH), α-enolase, neurofilament triplet L protein, glutathione S-transferase (GST) and fascin actin bundling protein were significantly reduced in brain of EA-treated dogs compared to control. We also observed significant increases in expression of Cu/Zn superoxide dismutase, fructose-bisphosphate aldolase C, creatine kinase, glutamate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The increased expression of these proteins and in particular Cu/Zn SOD correlated with improved cognitive function. In addition, there was a significant increas...

show abstract

Section: Discussionmentioning

confidence: 99%

Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: Relevance to Alzheimer's disease

Opii

Joshi

Head

et al. 2008

Neurobiology of Aging

Self Cite

175

135

View full text Add to dashboard Cite

show abstract

“…Aged dogs develop diffuse plaques and rarely exhibit neuritic plaques and neurofibrillary tangles (8,33). Aged bears develop both neuritic (senile) plaques and neurofibrillary tangles (7).…”

Section: 42 43mentioning

confidence: 99%

“…The aged beagle dog brain tissues examined in this study (Table 1) were obtained from the National Radiobiology Archives, as previously described (8,33). The animals received low levels of strontium-90 in their diet, but their longevity did not significantly differ from those of the control group.…”

Section: Aged Canine Tissuesmentioning

confidence: 99%

Carboxy terminal of β-amyloid deposits in aged human, canine, and polar bear brains

Tekirian

Cole

Russell

et al. 1996

Neurobiology of Aging

Self Cite

View full text Add to dashboard Cite

terminal of ~-amyloid deposits in human, canine, and polar bear brains. NEUROBIOL AGING 17(2) 249-257, 1996.--Immunocytochemistry, using antibodies specific for different carboxy termini of AI340 and AI342(43), was used to compare [3-amyloid deposits in aged animal models to nondemented and demented Alzheimer's disease human cases. Aged beagle dogs exhibit diffuse plaques in the absence of neurofibrillary pathology and the aged polar bear brains contain diffuse plaques and PHF-l-positiw~ neurofibrillary tangles. The brains of nondemented human subjects displayed abundant diffuse plaques, whereas the AD cases had both diffuse and mature (cored) neuritic plaques. Diffuse plaques were positively immunostained with an antibody against A[342(43) in all examined species, whereas AI340 immunopositive mature plaques were observed only in the human brain. Anti-Al~40 strongly immunolabeled cerebrovascular [3-amyloid deposits in each of the species examined, although some deposits in the polar bear brain were preferentially labeled with anti-A[342(43). [3-Amyloid deposition was evident in the outer molecular layer of the dentate gyrus in the aged dog, polar bear, and human. Within this layer, A1342 was present as diffuse deposits, although these deposits were morphologically distinct in each of the examined animal models. In dogs, A[342 was cloud-like in nature; the polar bear demonstrated a more aggregated type of deposition, and the nondemented human displayed well-defined deposits. Alzheimer's disease cases were most frequently marked by neuritic plaques in this region. Taken together, the data indicate that 13-amyloid deposition in aged mammals is similar to the earliest stages observed in human brain. In each species, AI342(43) is the initially deposited isoform in diffuse plaques.

show abstract

“…Several studies have shown that aged dogs naturally develop diffuse plaques that contain beta-amyloid (Aβ) peptide similar to those observed in humans with mild cognitive impairment and AD (Wisniewski et al 1990;Cummings et al 1993;Hou et al 1997;Head et al 2000). Further, dogs and humans express the same 1-42 amino acid sequence Aβ peptide (Selkoe et al 1987;Johnstone et al 1991).…”

Section: Why Study Aging In Dogs?mentioning

confidence: 89%

Strategies for improving cognition with aging: insights from a longitudinal study of antioxidant and behavioral enrichment in canines

Christie

Opii

Head

2008

AGE

View full text Add to dashboard Cite

Studies in humans suggest that lifestyle factors can have a beneficial impact on the risk for developing cognitive decline and dementia with age. There is growing evidence that maintaining a physically and intellectually active lifestyle can positively impact cognitive ability in older individuals. Dietary factors, such as the intake of antioxidants, may also prevent age-related cognitive decline. However, studies in humans are challenging; many variables cannot be controlled, making it difficult for researchers to determine the exact types and quantities of enrichment and dietary factors necessary for positive effects on cognition. Studies in animal models of human aging allow researchers to precisely control such variables, and can be used to assess the mechanisms and molecular pathways underlying any positive effects. Here we review the results of an intervention study using a canine model of human aging. The study was unique in that it compared the effects of dietary antioxidant supplementation alone and in combination with behavioral enrichment. We found that both interventions lead to improvements in cognitive ability in aged dogs; however, combining the treatments preserved cognition to a greater extent than either treatment alone. Overall, the results suggest that antioxidant supplementation and behavioral enrichment target separate yet complementary molecular pathways to improve cognition, and support the idea that combinations of treatments to improve cognition and slow brain aging will produce greater benefits than single interventions.

show abstract

β-Amyloid accumulation in aged canine brain: A model of early plaque formation in Alzheimer's disease

Cited by 184 publications

References 42 publications

Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: Relevance to Alzheimer's disease

Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: Relevance to Alzheimer's disease

Carboxy terminal of β-amyloid deposits in aged human, canine, and polar bear brains

Strategies for improving cognition with aging: insights from a longitudinal study of antioxidant and behavioral enrichment in canines

Contact Info

Product

Resources

About