Intra-Individual Stability of CSF Biomarkers for Alzheimer's Disease over Two Years

Abstract

This study examines the intra-individual stability of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) over 2 years in 83 patients with mild cognitive impairment (MCI) and 17 cognitively healthy control individuals. All participants underwent clinical and neuropsychological evaluation and lumbar puncture at baseline and after 2 years at a university hospital memory clinic. CSF was analyzed for total tau (T-tau), phospho-tau181 (P-tau181) and amyloid-β1−42 (Aβ1−42). During the 2-year observational time, 12 MCI patients progressed to AD and 3 progressed to vascular dementia, while 68 remained stable. Baseline T-tau and P-tau181 levels were elevated in the MCI-AD group as compared to the stable MCI patients and the control group (p < 0.01), while baseline Aβ1−42 levels were lower (p < 0.001). Stable MCI patients were biochemically indistinguishable from controls. The biomarker levels at baseline and after 2 years showed Pearson R values between 0.81 and 0.91 (p < 0.001) and coefficients of variation of 7.2 to 8.7%. In conclusion, intra-individual biomarker levels are remarkably stable over 2 years. Thus, even minor biochemical changes induced by treatment against AD should be detectable using these biomarkers, which bodes well for their usefulness as surrogate markers for drug efficacy in clinical trials.

Relationships between biomarkers in aging and dementia

“…However, the detection of strong associations despite this delay, and previous reports of stability of CSF measurements and PIB deposition over years [28][29][30] mitigates this problem. The use of a single averaged ROI for both the FDG and PIB measures is another limitation, because regional tracer uptake has clinical significance that may provide additional information.…”

Clinical Trial Designs in Amyotrophic Lateral Sclerosis: Does One Design Fit All?

“…Phosphorylated neurofilament heavy chain appears elevated at stable levels throughout the disease [19][20][21][22][23][24][25][26]. Neurofilament light chain in cerebrospinal fluid (CSF) appears to increase as ALS progresses [19,[27][28][29][30][31]. Urate, which is lower in people with ALS than in controls, could serve a predictive or prognostic role [32][33][34][35][36].…”

Miglustat Treatment May Reduce Cerebrospinal Fluid Levels of the Axonal Degeneration Marker Tau in Niemann–Pick Type C

“…First, T-tau is believed to correlate to the current rate of axonal loss, but not to the total sum of neurons that have been lost during the course of the disease. Levels may therefore be stable despite clinical progression, such as in AD Zetterberg et al 2007). If a treatment reduces neurodegeneration, T-tau will be expected to decrease corresponding to the treatment-induced lower rate of axonal loss, but not further.…”