Idiopathic normal-pressure hydrocephalus, cerebrospinal fluid biomarkers, and the cerebrospinal fluid tap test.
Cerebrospinal fluid (CSF) biomarkers, including soluble amyloid β-42 (Aβ-42) and phosphorylated-tau (P-tau), reflect core pathophysiological features of Alzheimer's disease (AD). AD is frequently a concomitant pathology in older patients with idiopathic normal-pressure hydrocephalus (iNPH), and somewhat similar altered CSF dynamics exist in both AD and iNPH. We therefore investigated relationships between lumbar CSF biomarkers Aβ-42 and P-tau and clinical parameters in iNPH patients, along with differences in these biomarkers between CSF tap test (CSFTT) responders and non-responders. Thirty-one iNPH patients (14 CSFTT responders and 17 CSFTT non-responders) were included in the final analysis. We found lower CSF Aβ-42 correlated with poor cognitive performance (r=0.687, p<0.001 for Korean Mini Mental State Examination; r=0.568, p=0.001 for Frontal Assessment Battery; r=-0.439, p=0.014 for iNPH grading scale [iNPHGS] cognitive score; r=-0.588, p=0.001 for Clinical Dementia Rating Scale), and lower CSF P-tau correlated with gait dysfunction (r=-0.624, p<0.001 for Timed Up and Go Test; r=-0.652, p<0.001 for 10meter walking test; r=-0.578, p=0.001 for Gait Status Scale; r=-0.543, p=0.002 for iNPHGS gait score). In subgroup analysis, CSF P-tau/Aβ-42 ratios were significantly higher in CSFTT non-responders compared to responders (p=0.027). Two conjectures are suggested. One, CSF biomarkers may play different and characteristic roles in relation to different iNPH symptoms such as cognition and gait. Two, comorbid AD pathology in iNPH patients may affect the response to the CSFTT. Larger studies using combinations of other biomarkers associated with AD would be necessary to evaluate these hypotheses.
Department of Neurology, Kyungpook National University School of Medicine, 50 Samdeok-dong 2-ga, Jung-gu, Daegu 700-721, South Korea.
Kyunghun
K
Kang
Department of Neurology, Kyungpook National University School of Medicine, 50 Samdeok-dong 2-ga, Jung-gu, Daegu 700-721, South Korea.
Pan-Woo
PW
Ko
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu, South Korea; Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu, South Korea.
Myungwon
M
Jin
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu, South Korea; Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu, South Korea.
Kyoungho
K
Suk
Department of Neurology, Kyungpook National University School of Medicine, 50 Samdeok-dong 2-ga, Jung-gu, Daegu 700-721, South Korea; Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu, South Korea. Electronic address: neuromd@knu.ac.kr.
Ho-Won
HW
Lee
D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000150:complications; D005260:Female; D020233:Gait Disorders, Neurologic / Q000134:cerebrospinal fluid / Q000150:complications; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000134:cerebrospinal fluid* / Q000150:complications; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D013129:Spinal Puncture / Q000379:methods*; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000378:metabolism
D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
Biomarker; Cerebrospinal fluid; Normal pressure hydrocephalus; Phosphorylated-tau; Predictive value of tests; β amyloid