Increasing CSF phospho-tau levels during cognitive decline and progression to dementia

Background Little is known about longitudinal changes of cerebrospinal fluid (CSF) biomarkers during cognitive decline in neurodegenerative disease progression. Objective To investigate longitudinal changes in CSF biomarkers – total-tau (T-tau), phospho-tau (P-tau) and β-amyloid (Aβ42) – during cognitive decline. Methods Forty memory clinic patients (47.5% females), aged 61.3 ± 7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3 ± 1.8. Patients were divided into three groups based on baseline memory functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment (NIM). Results There was a significant increase in P-tau in the SIM-group during follow-up, while P-tau in MIM and NIM did not change. Eighty-three percent of the SIM-patients converted to dementia (80% AD), while most MIM- and NIM-patients remained non-demented. T-tau- and Aβ42-levels did not change in any of the memory groups during follow-up. Conclusion Increasing P-tau levels during cognitive decline and conversion to dementia suggest that P-tau may be useful as a longitudinal marker of the neurodegenerative process.