ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
A two-year study with fibrillar beta-amyloid (Abeta) immunization in aged canines: effects on cognitive function and brain Abeta.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 103 citations in OpenAlex.
- Calcineurin/NFAT inhibitors maintain cognition in a preclinical prevention study in an aging canine model of Alzheimer disease.Neurobiology of aging · 2025Article
- Age-Related Brain Atrophy and the Positive Effects of Behavioral Enrichment in Middle-Aged Beagles.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Recent Advances in the Treatment and Management of Alzheimer's Disease: A Precision Medicine Perspective.Current topics in medicinal chemistry · 2024Review
- Review
- Autologous skin-derived neural precursor cell therapy reverses canine Alzheimer dementia-like syndrome in a proof of concept veterinary trial.Stem cell research & therapy · 2022Article
- Sphingolipids and DHA Improve Cognitive Deficits in Aged Beagle Dogs.Frontiers in veterinary science · 2022Article
- Tacrolimus Protects against Age-Associated Microstructural Changes in the Beagle Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Translational animal models for Alzheimer's disease: An Alzheimer's Association Business Consortium Think Tank.Alzheimer's & dementia (New York, N. Y.) · 2020Article
- Canine Cognitive Dysfunction and Alzheimer's Disease - Two Facets of the Same Disease?Frontiers in neuroscience · 2019Review
- Plant-based chimeric HPV-virus-like particles bearing amyloid-β epitopes elicit antibodies able to recognize amyloid plaques in APP-tg mouse and Alzheimer's disease brains.Inflammopharmacology · 2018Article
- Aptamers Selected for Recognizing Amyloid β-Protein-A Case for Cautious Optimism.International journal of molecular sciences · 2018Review
- Deletion of Specific Sphingolipids in Distinct Neurons Improves Spatial Memory in a Mouse Model of Alzheimer's Disease.Frontiers in molecular neuroscience · 2018Article
- Investigation of the Safety of Focused Ultrasound-Induced Blood-Brain Barrier Opening in a Natural Canine Model of Aging.Theranostics · 2017Article
- Aβ vaccination in combination with behavioral enrichment in aged beagles: effects on cognition, Aβ, and microhemorrhages.Neurobiology of aging · 2017Article
- Monoclonal antibodies against Aβ42 fibrils distinguish multiple aggregation state polymorphisms in vitro and in Alzheimer disease brain.The Journal of biological chemistry · 2014Article
- Exercise enhances memory consolidation in the aging brain.Frontiers in aging neuroscience · 2014Article
- Prevention approaches in a preclinical canine model of Alzheimer's disease: benefits and challenges.Frontiers in pharmacology · 2014Review
- A canine model of human aging and Alzheimer's disease.Biochimica et biophysica acta · 2013Review
- Pyroglutamate-Modified Amyloid Beta Peptides: Emerging Targets for Alzheimer´s Disease Immunotherapy.Current neuropharmacology · 2013Article
- PiB Fails to Map Amyloid Deposits in Cerebral Cortex of Aged Dogs with Canine Cognitive Dysfunction.Frontiers in aging neuroscience · 2013Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Aged canines (dogs) accumulate human-type beta-amyloid (Abeta) in diffuse plaques in the brain with parallel declines in cognitive function. We hypothesized that reducing Abeta in a therapeutic treatment study of aged dogs with preexisting Abeta pathology and cognitive deficits would lead to cognitive improvements. To test this hypothesis, we immunized aged beagles (8.4-12.4 years) with fibrillar Abeta(1-42) formulated with aluminum salt (Alum) for 2.4 years (25 vaccinations). Cognitive testing during this time revealed no improvement in measures of learning, spatial attention, or spatial memory. After extended treatment (22 vaccinations), we observed maintenance of prefrontal-dependent reversal learning ability. In the brain, levels of soluble and insoluble Abeta(1-40) and Abeta(1-42) and the extent of diffuse plaque accumulation was significantly decreased in several cortical regions, with preferential reductions in the prefrontal cortex, which is associated with a maintenance of cognition. However, the amount of soluble oligomers remained unchanged. The extent of prefrontal Abeta was correlated with frontal function and serum anti-Abeta antibody titers. Thus, reducing total Abeta may be of limited therapeutic benefit to recovery of cognitive decline in a higher mammalian model of human brain aging and disease. Immunizing animals before extensive Abeta deposition and cognitive decline to prevent oligomeric or fibrillar Abeta formation may have a greater impact on cognition and also more directly evaluate the role of Abeta on cognition in canines. Alternatively, clearing preexisting Abeta from the brain in a treatment study may be more efficacious for cognition if combined with a second intervention that restores neuron health.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.