Aβ peptides as one of the crucial volume transmission signals in the trophic units and their interactions with homocysteine. Physiological implications and relevance for Alzheimer's disease

Amyloid peptides (Aβ) can operate as volume transmission (VT) signals since they are continuously released from cells of the central nervous system and diffuse in the extra-cellular space of the brain. They have both regulatory and trophic functions on cellular networks. In agreement with Aβ regulatory actions on glial-neuronal networks, the present paper reports new findings demonstrating that intrastriatal injections of Aβ peptides reduce striatal tyrosine hydroxylase, increase striatal GFAP immunoreactivities and lower pain threshold in experimental rats. Furthermore, it has been demonstrated that exogenous homocysteine (Hcy) binds Aβ(1-40) favouring its β-sheet conformation both in vitro and in vivo and hence the formation of β-fibrils and development of neurotoxicity. Thus, the hypothesis is discussed that Aβ peptides represent crucial VT-signals in the brain and their action is altered by dysmetabolic signals such as high Hcy extra-cellular levels, known to be an important risk factor for Alzheimer's disease.