Age-specific onset of β-amyloid in Beagle brains

Russell, Michael J.; Bobik, Marketta; White, R. G.; Hou, Yang; Benjamin, Stephen A.; Geddes, James W.

doi:10.1016/0197-4580(95)02072-1

Cited by 31 publications

(20 citation statements)

References 22 publications

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“…Though this progression in dogs is similar to that reported in humans, it is not identical. In canines, the accumulation of Aβ begins in the prefrontal cortex (approximately 8 years at age of onset) and continues to develop with increasing age to include other regions such as the temporal and occipital cortex (Russell et al, 1996; Head et al, 2000; Cotman and Head, 2008). The severity of neuropathology can vary between individual animals but can be linked to the extent of cognitive decline (Cummings et al, 1996a; Head et al, 1998b; Colle et al, 2000; Rofina et al, 2006).…”

Section: Dog Neuropathology and Outcome Measures For Prevention Studiesmentioning

confidence: 99%

Prevention approaches in a preclinical canine model of Alzheimerâ€™s disease: benefits and challenges

Davis

Head

2014

Front. Pharmacol.

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Aged dogs spontaneously develop many features of human aging and Alzheimer’s disease (AD) including cognitive decline and neuropathology. In this review, we discuss age-dependent learning tasks, memory tasks, and functional measures that can be used in aged dogs for sensitive treatment outcome measures. Neuropathology that is linked to cognitive decline is described along with examples of treatment studies that show reduced neuropathology in aging dogs (dietary manipulations, behavioral enrichment, immunotherapy, and statins). Studies in canine show that multi-targeted approaches may be more beneficial than single pathway manipulations (e.g., antioxidants combined with behavioral enrichment). Aging canine studies show good predictive validity for human clinical trials outcomes (e.g., immunotherapy) and several interventions tested in dogs strongly support a prevention approach (e.g., immunotherapy and statins). Further, dogs are ideally suited for prevention studies as they the age because onset of cognitive decline and neuropathology strongly support longitudinal interventions that can be completed within a 3–5 year period. Disadvantages to using the canine model are that they lengthy, use labor-intensive comprehensive cognitive testing, and involve costly housing (almost as high as that of non-human primates). However, overall, using the dog as a preclinical model for testing preventive approaches for AD may complement work in rodents and non-human primates.

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Section: Dog Neuropathology and Outcome Measures For Prevention Studiesmentioning

confidence: 99%

Prevention approaches in a preclinical canine model of Alzheimerâ€™s disease: benefits and challenges

Davis

Head

2014

Front. Pharmacol.

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“…In aged dogs, beta-amyloid accumulation correlates with cognitive dysfunction; plaques are of the diffuse subtype; and there is no neuritic involvement (36). A threshold effect of plaque development was observed by Russell (99) in 103 laboratory-raised beagles. In dogs kept in outdoor kennels at Davis, CA, and Fort Collins, CO, no plaques were apparent at ages younger than 10 years, but numbers progressively increased to 73% at ages 15 to 17.8 years (99).…”

Section: Introductionmentioning

confidence: 99%

“…A threshold effect of plaque development was observed by Russell (99) in 103 laboratory-raised beagles. In dogs kept in outdoor kennels at Davis, CA, and Fort Collins, CO, no plaques were apparent at ages younger than 10 years, but numbers progressively increased to 73% at ages 15 to 17.8 years (99). Weigel (111) described in a cohort of 30 mongrel dogs a subpopulation with increased numbers of b -amyloid-positive diffuse plaques and concluded that only 43% of these mongrel dogs were susceptible to amyloidosis or that only the severely affected subpopulation was exposed to a factor or factors inducing this pathology.…”

Section: Introductionmentioning

confidence: 99%

Air Pollution and Brain Damage

et al. 2002

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Exposure to complex mixtures of air pollutants produces in ammation in the upper and lower respiratory tract. Because the nasal cavity is a common portal of entry, respiratory and olfactory epithelia are vulnerable targets for toxicological damage. This study has evaluated, by light and electron microscopy and immunohistochemica l expression of nuclear factor-kappa beta (NF-j B) and inducible nitric oxide synthase (iNOS), the olfactory and respiratory nasal mucosae, olfactory bulb, and cortical and subcortical structures from 32 healthy mongrel canine residents in Southwest Metropolitan Mexico City (SWMMC), a highly polluted urban region. Findings were compared to those in 8 dogs from Tlaxcala, a less polluted, control city. In SWMMC dogs, expression of nuclear neuronal NF-j B and iNOS in cortical endothelial cells occurred at ages 2 and 4 weeks; subsequen t damage included alterations of the blood-brain barrier (BBB), degenerating cortical neurons, apoptotic glial white matter cells, deposition of apolipoprotein E (apoE)-positive lipid droplets in smooth muscle cells and pericytes, nonneuritic plaques, and neuro brillary tangles. Persistent pulmonary in ammation and deteriorating olfactory and respiratory barriers may play a role in the neuropatholog y observed in the brains of these highly exposed canines. Neurodegenerativ e disorders such as Alzheimer's may begin early in life with air pollutants playing a crucial role.

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“…Dog with cognitive dysfunction syndrome (CDS) is considered a suitable model to address these innovative therapies [13], because it spontaneously expresses several markers associated with the underlying pathology of sporadic AD. Control aged dog (over 7-8 years) is also considered quite unique to elucidate the amyloid hypothesis, since its CNS Aβ peptide accumulation is responsible for neuronal dysfunction and deregulation of the same specific cortical subsets of interneurons described in the aged human [14][15][16][17]. In addition, these aged animals also bring multiple druggable targets for the identification of novel disease-modifying agents to interfere natural Aβ production, aggregation, clearance or the associated neurotoxic effects [18,19].…”

Section: Introductionmentioning

confidence: 99%

Rapid Improvement of Canine Cognitive Dysfunction with Immunotherapy designed for Alzheimer's Disease

Bosch¹,

Bayon²,

Rodrı́guez³

et al. 2013

CAR

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ABSTRACT:Immunotherapy against amyloid-beta (Aβ) may improve rodent cognitive function by reducing amyloid neuropathology and is being validated in clinical trials with positive preliminary results. However, for a complete understanding of the direct and long-term immunization responses in the aged patient, and also to avoid significant side effects, several key aspects remain to be clarified. Thus, to investigate brain Aβ clearance and Th2 responses in the elderly, and the reverse inflammatory events not found in the immunized rodent, better Alzheimer's disease (AD) models are required. In the aged familiar canine with a cognitive dysfunction syndrome (CDS) we describe the rapid effectiveness and the full safety profile of a new active vaccine candidate for human AD prevention and treatment. In these aged animals, besides a weak immune system, the antibody response activated a coordinated central and peripheral Aβ clearance, that rapidly improved their cognitive function in absence of any side effects. Our results also confirm the interest to use familiar dogs to develop innovative and reliable therapies for AD.

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Age-specific onset of β-amyloid in Beagle brains

Cited by 31 publications

References 22 publications

Prevention approaches in a preclinical canine model of Alzheimerâ€™s disease: benefits and challenges

Prevention approaches in a preclinical canine model of Alzheimerâ€™s disease: benefits and challenges

Air Pollution and Brain Damage

Rapid Improvement of Canine Cognitive Dysfunction with Immunotherapy designed for Alzheimer's Disease

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