New insights into brain BDNF function in normal aging and Alzheimer disease

The decline observed during aging involves multiple factors that influence several systems. it is the case for learning and memory processes which are severely reduced with aging. it is admitted that these cognitive effects result from impaired neuronal plasticity, which is altered in normal aging but mainly in Alzheimer disease. Neurotrophins and their receptors, notably BDNF, are expressed in brain areas exhibiting a high degree of plasticity (i.e. the hippocampus, cerebral cortex) and are considered as genuine molecular mediators of functional and morphological synaptic plasticity. Modification of BDNF and/or the expression of its receptors (TrkB.FL, TrkB.T1 and TrkB.T2) have been described during normal aging and Alzheimer disease. Interestingly, recent findings show that some physiologic or pathologic age-associated changes in the central nervous system could be offset by administration of exogenous BDNF and/or by stimulating its receptor expression. These molecules may thus represent a physiological reserve which could determine physiological or pathological aging. These data suggest that boosting the Expression or activity of these endogenous protective systems may be a promising therapeutic alternative to enhance healthy aging. (C) 2008 Elsevier B.V. All rights reserved