ABSTRACT
Immunotherapy against amyloid-ß(Aß) 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 Aß 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, besidesa weak immune system, the antibody response activated a coordinated central and peripheral Aß 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.
Subject(s)
Alzheimer Disease/complications , Alzheimer Disease/therapy , Cognition Disorders/etiology , Cognition Disorders/therapy , Immunotherapy/methods , Age Factors , Aging/immunology , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/immunology , Amyloid beta-Peptides/blood , Amyloid beta-Peptides/cerebrospinal fluid , Amyloid beta-Peptides/immunology , Analysis of Variance , Animals , Disease Models, Animal , Dogs , Eliminative Behavior, Animal , Expressed Emotion , Female , Hematologic Tests , Humans , Immunoglobulin G/therapeutic use , Male , Peptide Fragments/blood , Peptide Fragments/cerebrospinal fluid , Rabbits , WalkingABSTRACT
In the search for appropriate models for Alzheimer's disease (AD) involving animals other than rodents, several laboratories are working with animals that naturally develop cognitive dysfunction. Among the animals tested, dogs are quite unique in helping to elucidate the cascade of events that take place in brain amyloid-beta (Aß)deposition aging, and cognitive deficit. Recent innovative research has validated human methods and tools for the analysis of canine neuropathology and has allowed the development of two different approaches to investigate dogs as natural models of AD. The first approach relates AD-like neuropathy with the decline in memory and learning ability in aged housed dogs in a highly controlled laboratory environment. The second approach involves research in family-owned animals with cognitive dysfunction syndrome. In this review, we compare the strengths and limitations of housed and family-owned canine models, and appraise their usefulness for deciphering the early mechanisms of AD and developing innovative therapies.
