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

Sci Rep. 2020 Jun 4;10(1):9106. doi: 10.1038/s41598-020-66154-y.

Abstract

Our study aimed to: 1)investigate the diagnostic utility of CSF Aβ42, 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 Aβ42 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 ± 13.3 pg/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 ± 311.5 pg/mL; respectively) but the CSF-Aβ42 was low in both the probable-NPH and AD. CSF-Aβ42 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 Aβ42 clearance in the CSF because of the increase in the interstitial space.

MeSH terms

  • Aged
  • Aging / pathology*
  • Alzheimer Disease / diagnosis
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Amyloid beta-Peptides / metabolism
  • Atrophy
  • Biomarkers / cerebrospinal fluid
  • Brain / metabolism
  • Brain / pathology*
  • Diagnosis, Differential
  • Female
  • Humans
  • Hydrocephalus, Normal Pressure / diagnosis*
  • Male
  • Peptide Fragments / cerebrospinal fluid*
  • Peptide Fragments / metabolism

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)