J Neurol Neurosurg Psychiatry 2001;70:624-630 ( May )

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

M Sjögren^a, P Davidsson^a, M Tullberg^a, L Minthon^b, A Wallin^a, C Wikkelso^a, A-K Granérus^c, H Vanderstichele^d, E Vanmechelen^d, K Blennow^{a e}

^a Institute of Clinical Neuroscience, Göteborg University, Sahlgrenska University Hospital / Mölndal, Sweden, ^b Department of Community Medicine, Lund University, Neuropsychiatric Clinic, Malmö University Hospital, Malmö, Sweden, ^c Department of Geriatrics, University of Health Sciences, Linköping, Sweden, ^d Innogenetics, Ghent, Belgium, ^e Medical Research Council, Sweden

Correspondence to: Dr M Sjögren, Institute of Clinical Neuroscience, Sahlgrenska Universitetssjukhuset Mölndal, SE 431 80 Mölndal, Sweden magnus.sjogren{at}medfak.gu.se

Received 6 October 2000 and in revised form 15 December 2000; Accepted 19 December 2000

BACKROUNDPathological 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 tau pathology in AD differs from that in FTD and that the difference may be related to the degree of phosphorylation. As CSF tau protein is increased after stroke, tau may also be implicated in the pathophysiology of vascular dementia, of which subcortical arteriosclerotic encephalopathy (SAE) is a putative subtype.
OBJECTIVESTo investigate the nature of tau protein in CSF and the involvement of total CSF tau and phosphorylated CSF tau (phosphotau) in various types of dementia.
METHODSUsing ELISAs for total tau and tau phosphorylated at Thr181 (phosphotau), the CSF concentrations of total tau and phosphotau were determined in 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 controls (n=17). All the antibodies stained the lower molecular weight bands, whereas only the antibodies that recognise phosphorylated tau stained the higher molecular bands.
RESULTSBoth CSF tau and CSF phosphotau were increased in probable AD compared with FTD (p<0.001), SAE (p<0.001), PD (p<0.001), and controls (p<0.001). CSF phosphotau was increased in possible AD compared with FTD (p<0.001) and SAE (p<0.001). CSF tau and CSF phosphotau were positively correlated in all the groups. Molecular weight forms of tau ranging from 25 kDa to 80 kDa were found in the CSF
CONCLUSIONBoth phosphorylated and unphosphorylated tau isoforms were present in the CSF, and tau protein appeared in both truncated and full length forms. 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 in the normal range do not exclude AD.


Keywords: cerebrospinal fluid; tau; hyperphosphorylated tau

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© 2001 by Journal of Neurology, Neurosurgery, and Psychiatry
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