Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer's disease: a community based follow up study

摘要

OBJECTIVES—Biochemical markers for Alzheimer'sdisease would be of great value, especially to help in diagnosis earlyin the course of the disease. A pronounced increase in CSF tau protein(CSF-tau) is found in most patients with Alzheimer's disease. However,the specificity has to be further studied, as an increase in CSF-tau has also been found in other dementias, especially in vascular dementia. As most previous CSF studies have been based on selected inpatients, it was considered of special interest to examine the diagnostic potential of CSF-tau in a community population based sampleof consecutive patients with dementia. Such patient material has beenexamined at the Piteå River Valley Hospital in Northern Sweden since1986, and includes all those with memory disturbances in the community.The aim was also to study if an increase in CSF-tau is found early inthe disease process, and whether CSF-tau changes during the progressionof disease.
METHODS—Participants: Community population basedsample of 75 demented patients (43 with Alzheimer's disease, 21 withvascular dementia, and 11 with mixed Alzheimer's disease/vasculardementia), 18 healthy subjects, and 18 neurological controls. A followup investigation (including analysis of a new CSF sample) was performedin all patients after about one year.
MAIN OUTCOME MEASURES—Concentrations of total(both normal tau and PHF-tau) tau in CSF, clinical measures (durationand severity of dementia), and apoE polymorphism.
RESULTS—CSF-tau was markedly increased inAlzheimer's disease, 41/43 (95%) patients had values above the cutoff level (mean+2 SD) in controls (306 pg/ml). High CSF-tauconcentrations were also found in most patients withvascular dementia, preferentially in patients with vascular dementiawithout progressive leukoaraiosis on CT, whereas patients with vasculardementia with progressive leukoaraiosis had normal CSF-tau.Concentrations of CSF-tau were stable at one year followup in both patients with Alzheimer's disease and patients withvascular dementia, and there was no correlation between CSF-tau andeither duration or severity of dementia.
CONCLUSIONS—The findings confirm the highsensitivity of CSF-tau for the diagnosis of Alzheimer's disease, buthigh CSF-tau was also found in vascular dementia, resulting in a lowerspecificity. However, high CSF-tau is preferentially found in patientswith vascular dementia without progressive leukoaraiosis,which may constitute a group with concomitant Alzheimer's diseasepathology. High CSF-tau may be present during the whole course of thedisease in Alzheimer's disease. Possibly, therefore, the same highCSF-tau concentrations may be present before the onset of clinicaldementia. Follow up studies on such patients will tell whether analysisof CSF-tau is useful as a biochemical marker for early Alzheimer's disease.