Apports de la biologie dans le diagnostic des démences

Since 2007, the combined dosage of three biomarkers in the cerebrospinal fluid has been considered an essential component of procedures to help establish a diagnosis of Alzheimer’s disease (AD). These biomarkers include total-Tau proteins, phosphorylated variants of Tau and amyloid-beta peptides. Their levels are altered early during the course of AD but they are not useful for a differential diagnosis of other dementing disorders. Perspectives therefore focus on finding plasmatic biomarkers and developing new biomarkers that would aid discrimination between dementing disorders.     

Volume-activated Na/H exchange activity in fetal and adult pig red cells: Inhibition by cyclic AMP

Summary Hyposmotic swelling of pig red cells leads to a selective increase in K permeability, whereas hyperosmotic cell shrinkage augments the Na permeability. In this regard, the ouabain-resistant (OR) Na flux of red cells of newborn and adult pigs is characterized in detail. A reduction in cell volume by approximately 18% leads to an increase in the OR Na efflux of fetal and adult cells by 15-and fourfold, respectively. The OR Na influx in both cell types is equally influenced by cell shrinkage. Depletion of cellular K does not influence the volume-activated OR Na efflux. Nor does OR Na influx require external K. Both OR Na efflux and influx activated by shrinkage are inhibited by the diuretics furosemide and amiloride. The rank order of decreasing anion sensitivity for diuretic-sensitive Na efflux was acetate > chloride > gluconate > nitrate. Cell shrinkage induced by the addition of hypertonic salts results in an acidification of the unbuffered and CO₂-free media, provided that both Na and DIDS are present. The qcidification process can be reversed by either of the diuretic agents. These findings suggest that the shrinkageactivated OR Na flux is primarily mediated by a Na/H exchanger rather than by a Na/K/Cl cotransporter. Once loaded with either cAMP or cGMP, cell swelling can no longer activate the Na/H exchanger. The Na/H exchanger activity is detectable in the fetal cells of normal volume but quiescent in adult cells, indicating that the exchanger undergoes a developmental change during the transition from the fetal to adult stage.