Association Between Cerebrospinal Fluid Biomarkers and Age-related Brain Changes in Patients with Normal Pressure Hydrocephalus

Our study aimed to: 1)investigate the diagnostic utility of CSF A beta 42, t-tau, and p-tau to differentiate normal-pressure-hydrocephalus(NPH) from Alzheimer's-disease(AD) and normal-controls; and 2)investigate if age and ventricular size affect the levels of CSF biomarkers in NPH patients. We recruited 131 participants: (a)Suspected-NPH: 72 with ventriculomegaly and clinical symptoms of NPH. These participants were then divided into two groups of 1)Probable-NPH (N=38) and 2)Unlikely-NPH (N=34) based on whether participants experienced gait improvement after removal of a large amount of CSF; (b)AD group: 30 participants with CSF biomarkers and cognitive symptoms consistent with AD; (c)Control-group: 29 participants who were cognitively and functionally normal. Lower levels of CSF A beta 42 and p-tau were observed in the probable-NPH compared to the normal controls(444.22 +/- 163.3 vs. 1213.75 +/- 556.5; and 26.05 +/- 9.2 vs. 46.16 +/- 13.3pg/mL; respectively). Lower levels of CSF p-tau and t-tau were found in the probable-NPH compared to the AD(26.05 +/- 9.2 vs. 114.95 +/- 28.2; and 193.29 +/- 92.3 vs. 822.65 +/- 311.5pg/mL; respectively) but the CSF-A beta 42 was low in both the probable-NPH and AD. CSF-A beta 42 correlated with age and Evans-index only in the probable-NPH(r=0.460, p=0.004; and r=-0.530, p=0.001; respectively). Our study supports the hypothesis that age-related atrophy results in better A beta 42 clearance in the CSF because of the increase in the interstitial space.