We will discuss the FAB rat in more detail below. Other amyloid species used included AB25 35, a neurotoxic non amyloidogenic fragment, and AB1 43. phosphatase inhibitor These various amyloid fragments did not induce similar pathological phenotypes. While histological alterations similar to those seen in AD patients were consistently found in most of the models, reproducing the decline of cognitive performance was highly dependent on the experimental protocol. The amyloid peptide infusion site and regimen used were of particular importance. Another strategy developed during this decade was based on the hypothesis that AD may be a type 3 diabetes. This hypothesis was based on post mortem histological observations of the brains of AD patients, which showed a consistent decrease in expression of insulin, insulin like growth factor, and their corresponding receptors.

It was then assumed that injecting streptozotocin, a glucosaminenitrosourea toxic to pancreatic B cells, into rat brain would result in the same pattern. Streptozotocin administration induced the phosphorylation of the tau protein, amyloid deposits, cognitive impairment, Inhibitors,Modulators,Libraries insulin desensitization, and neuronal death. he beginning of the current decade saw an increasing number of preclinical studies Inhibitors,Modulators,Libraries using AD rat models characterized during the 2000s to implement drug development programs. In particular, rat models faith fully reproducing amyloid pathogenesis were used to assess the e?cacy of drug candidates as diverse Inhibitors,Modulators,Libraries as steroid analogs, fatty acids, polyphenols, non steroidal anti in?ammatory drugs, plant extracts, secretase inhibitor, stem cell proliferative agents, naturally occurring compounds, and plaque formation inhibitors.

Other than the type of amyloid peptide used in these models, a major di?erence was the injection regimen into the brain. The solution containing the amyloid Inhibitors,Modulators,Libraries peptide was adminis tered either by chronic infusion Inhibitors,Modulators,Libraries or locally in a very speci?c part of the brain, mainly the hippocampus. Intra amygdala selleck chem injection or acute intracerebroventricular injection have also been reported. Chronic infusion was achieved through intracerebroventricular administration using an Alzet type of osmotic micropump, generally over a 2 to 4 week period of time. The resurgence of interest in the rat as an animal model of AD led other investigators to use various other types of rat models to investigate the e?ect of molecules of potential therapeutic interest. These models included, but were not restricted to, speci?c cholinergic de?cits, streptozotocin injections, okadaic acid induced tau protein hyperphos phorylation, and aluminum salt administration.