Victims of Alzheimer's disease (AD) develop a progressive dementia over years, accompanied by development of neurofibrillary tangles and finally neuronal death, accumulation of amyloid plaques and deposition of amyloid in neuro-vessels. Currently AD is the major form of dementia and the fourth leading cause of death in aged population. The investigation of etiology and therapy of AD, now more than ever, needs an infusion of new concepts. The aims of this review are to analyze knowledge of the influence of ischaemic and amyloid pathology on the final development of AD, especially with regards to the etiology of AD plaques, to develop a consensus on whether ischaemic blood-brain barrier permeability for amyloid peptide or both are a valid target for AD therapy. Reviewing experimental models of AD, we will address the issue whether plaques of amyloid persist, develop with time or both in animals during different forms of experimental therapy. Based on above suggestions recent direct evidence that amyloid plaques and neuro-fibrillary tangles can be cleared from the brain is thus provided in experimental condition. Moreover, recent study provides data that immunization with -amyloid peptide decreases blood-brain barrier permeability for -amyloid peptide or restores blood-brain barrier integrity. This review summarizes the latest advances in this area focusing on investigations based on in vivo animal studies.