Both total and phosphorylated tau are increased in Alzheimer's disease

Background-Pathological tau protein concentrations in CSF are found in both Alzheimer's disease (AD) and frontotemporal dementia (FTD), but studies on brain tissue have suggested that the tall pathology in XD differs from tha t in FTD and that the difference may be related to the degree of phosphoryl ation,;Is CSF tau protein is increased after stroke, tau may also be implic ated in the pathophysiology of vascular dementia, of which subcortical arte riosclerotic encephalopathy (SAE) is a putative subtype. Objectives-To investigate the nature of tau protein in CSF and the involvem ent of total CSF tau and phosphorylated CSF tau (phosphotau) in various typ es of dementia. Methods-Using ELISAs for total tau and tau phosphorylated at Thr181 (phosph otau), the CSF concentrations of total tau and phosphotau were determined i n patients with probable and possible AD (n= 41 and 19, respectively), FTD (n=18), SAE (n=17), and Parkinson's disease (PD; n=15) and in age matched c ontrols (n=17). All the antibodies stained the lower molecular weight bands , whereas only the antibodies that recognise phosphorylated tau stained the higher molecular bands. Results-Both CSF tau and CSF phosphotau were increased in probable, AD comp ared (p <0.001), PD (p <0.001), and controls (p <0.001). CSF phosphotau was increased in possible AD compared with FTB (p <0.001) and SAE (p <0.001). CSF tau and CSF phosphotau were positively correlated in all the groups. Mo lecular weight farms of tau ranging from 25 kDa to 80 kDa were found in the CSF Conclusion-Both phosphorylated and unphosphorylated tau isoforms mere prese nt in the CSF, and tau protein appeared in both truncated and full length f orms. The results suggest that the CSF concentrations of tau and phosphotau are increased in about two thirds of patients with probable AD and in half of those with possible AD but are normal in FTD, SAE, and PD compared with normal aging. Values ill the normal range do not exclude AD.