Journal of Alzheimer's Disease - Volume 15, issue 4

Authors: Coico, Richard | Woodruff-Pak, Diana S.

Article Type: Research Article

Abstract: This timely special issue of the Journal of Alzheimer's Disease provides the opportunity to examine interfaces between basic science and clinical medicine using animal models to develop more effective therapies for the treatment and, ideally, prevention of Alzheimer's disease (AD). That some patients with AD enrolled in a clinical trial to inoculate against amyloid-β (Aβ) experienced a misdirected polarization of Th cells reminds us that our knowledge of T cell biology, immune regulation, and the precise functional properties of adjuvants is incomplete. We review this knowledge and consider the advantages of the rabbit for immunological studies. The langomorph species is …proximate to primates on the phylogenetic scale, its amino acid sequence of Aβ is 97% identical to the human Aβ sequence, and the rabbit model system is extensively characterized on a form of associative learning with parallels in normal aging in rabbits and humans that is severely impaired in human AD. Cholesterol-fed rabbits treated with Aβ immunotherapy generate high titer anti-Aβ responses. The cholesterol-fed rabbit model of AD with its close parallels to human genetics and physiology, along with its validity from molecular to cognitive levels as a model of human AD, provides a promising vehicle for development of immunotherapies. Show more

Keywords: Amyloid-β, immunotherapy, rabbit model, T cell biology

DOI: 10.3233/JAD-2008-15411

Citation: Journal of Alzheimer's Disease, vol. 15, no. 4, pp. 657-671, 2008

Authors: Ghribi, Othman

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF has been watermarked “RETRACTED”. A retraction notice is available at DOI: 10.3233/JAD-239016 .

DOI: 10.3233/JAD-2008-15412

Citation: Journal of Alzheimer's Disease, vol. 15, no. 4, pp. 673-684, 2008

Authors: Cotman, Carl W. | Head, Elizabeth

Article Type: Research Article

Abstract: Aged dogs (beagles) develop losses in executive function, learning and memory. The severity of decline in these cognitive domains represents a spectrum that captures normal aging, mild cognitive impairment and early/mild Alzheimer's disease (AD) in humans. In parallel, dogs naturally accumulate several types of neuropathology (although not all) consistent with human brain aging and AD including cortical atrophy, neuron loss, loss of neurogenesis, amyloid-β (Aβ) plaques, cerebral amyloid angiopathy and oxidative damage. Many of these neuropathological features correlate with the extent of cognitive decline in a brain region-dependent manner. Dogs are ideally suited for longitudinal studies, and we provide a …summary of the beneficial effects of an antioxidant diet, behavioral enrichment, and Aβ immunotherapy. In addition, combinatorial treatment approaches can be a powerful strategy for improving brain function through enhancement of multiple molecular pathways. Show more

Keywords: Amyloid-β, antioxidants, beagle, behavioral enrichment, immunotherapy, learning, memory, neuron loss

DOI: 10.3233/JAD-2008-15413

Citation: Journal of Alzheimer's Disease, vol. 15, no. 4, pp. 685-707, 2008

Authors: Buccafusco, Jerry J.

Article Type: Research Article

Abstract: Non-human primates have served as subjects for studies of the cognition-enhancing potential of novel pharmacological agents for over 25 years. Only recently has a greater appreciation of the translational applicability of this model been realized. Though most Old-World monkeys do not appear to acquire an Alzheimer's-like syndrome in old age, their value resides in the brain physiology they have in common with humans. Paradigms like the delayed matching-to-sample task engender behavior that models aspects of working memory that are substrates for the actions of cognition-enhancing drugs. Our studies have provided information relevant to factors that limit the effectiveness of clinical …trial design for compounds that potentially improve cognition. For example, cognition-enhancing compounds from different pharmacological classes, when administered to monkeys, can exhibit remarkable pharmacodynamic effects that outlast the presence of the drug in the body. Studies with non-human primates also can provide information regarding dose ranges and individual subject sensitivity experienced in the clinic. Components of working memory are differentially sensitive to drug effects and may be characterized by different dose ranges for certain compounds, even within the same task. Examples are provided that underscore the possible idiosyncrasies of drug action in the pharmacology of cognition – which could be of critical importance in the design of clinical trials. Show more

Keywords: Acetylcholinesterase inhibition, aging, Alzheimer's disease, attention deficit disorder, delayed matching, drug development, nicotinic acetylcholine receptors, non-human primates, working memory

DOI: 10.3233/JAD-2008-15414

Citation: Journal of Alzheimer's Disease, vol. 15, no. 4, pp. 709-720, 2008

Article Type: Other

DOI: 10.3233/JAD-2008-15415

Citation: Journal of Alzheimer's Disease, vol. 15, no. 4, pp. 721-723, 2008

Article Type: Announcement

DOI: 10.3233/JAD-2008-15416

Citation: Journal of Alzheimer's Disease, vol. 15, no. 4, pp. 725-726, 2008