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 (A beta ) 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 A beta regulatory actions on glial-neuronal networks, the present paper reports new findings demonstrating that intrastriatal injections of A beta 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 A beta (1-40) favouring its beta -sheet conformation both in vitro and in vivo and hence the formation of beta -fibrils and development of neurotoxicity. Thus, the hypothesis is discussed that A beta 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.