The vascular component of Alzheimer's disease

Cognitive abilities depend primarily on cerebrovascular health and aging. In this work, we examine the pathogenic mechanisms of brain dysfunction linked to vascular risk factors, insulin signaling and cerebrovascular damage and explore how these mechanisms interfere with neurodegeneration. Although Abeta hypothesis prevails in the ethiology of Alzheimer's Disease (AD), it has become increasingly evident that disturbances in cerebral glucose metabolism is an invariant pathophysiological feature of AD and may provide an ubiquituos mechanism underlying the pathogenesis of AD. Currently, it is difficult to identify efficient therapeutic approach for brain protection and recovery, especially because we do not fully understand the underlying neurobiological processes, the nature of the pathophysiological mechanisms and the links between these two categories. Endogenous neurobiological processes, such as "brain reserves", neurotrophicity, neuroplasticity and neurogenesis, are central to protection and recovery and represent the background of endogenous defense activity (EDA). The historical concept of neuroprotection being the suppression of pathophysiological processes by a single mechanism or molecule may have been effective in clinical practice, but is now obsolete and indicates a failure of the reductionist approach to neuroprotection in the clinical setting. Pharmacological intervention should address modulation not suppression. The more pathophysiological processes are modulated, the better the chances are for therapeutic success in brain protection and recovery. Therefore, drugs with pleiotropic neuroprotective mechanisms of action are the best candidates for acute neuroprotection.