Immunotherapy for Alzheimer's disease: Harnessing our knowledge of T cell biology using a cholesterol-fed rabbit model

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.