J Clin Neurol.  2019 Jul;15(3):353-359. 10.3988/jcn.2019.15.3.353.

Cerebrospinal Fluid Levels of β-Amyloid 40 and β-Amyloid 42 are Proportionately Decreased in Amyloid Positron-Emission Tomography Negative Idiopathic Normal-Pressure Hydrocephalus Patients

Affiliations
  • 1Department of Neurology, Ajou University School of Medicine, Suwon, Korea. symoon.bv@gmail.com
  • 2Department of Brain Science, Ajou University School of Medicine, Suwon, Korea. jaerakchang@ajou.ac.kr
  • 3Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Korea.
  • 4Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Suwon, Korea.
  • 5Department of Neurology, Chung-Ang University College of Medicine, Seoul, Korea.
  • 6Department of Anatomy, Ajou University School of Medicine, Suwon, Korea.

Abstract

BACKGROUND AND PURPOSE
Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) could be misleading in idiopathic normal-pressure hydrocephalus (iNPH). We therefore investigated the CSF biomarkers in 18F-florbetaben amyloid-negative positron-emission tomography (PET) [amyloid PET(−)] iNPH, amyloid-positive PET [amyloid PET(+)] AD, and cognitively normal (CN) subjects.
METHODS
Ten amyloid PET(+) AD patients (56.7±5.6 years old, mean±standard deviation), 10 amyloid PET(−) iNPH patients (72.8±4.5 years old), and 8 CN subjects (61.2±6.5 years old) were included. We measured the levels of β-amyloid (Aβ)40, Aβ42, total tau (t-tau) protein, and phosphorylated tau (p-tau) protein in the CSF using enzyme-linked immunosorbent assays.
RESULTS
The level of Aβ42 and the Aβ42/Aβ40 ratio in the CSF were significantly lower in AD than in iNPH or CN subjects. The Aβ40 level did not differ significantly between AD and iNPH (p=1.000), but it did between AD and CN subjects (p=0.032). The levels of both t-tau and p-tau were higher in AD than in iNPH or CN subjects. The levels of Aβ42, Aβ40, t-tau, and p-tau were lower in iNPH than in CN subjects, but there was no significant difference after controlling for age.
CONCLUSIONS
Our results suggest that the mechanism underlying low CSF Aβ levels differs between amyloid PET(−) iNPH and amyloid PET(+) AD subjects. The lower levels of all CSF biomarkers in iNPH patients might be due to reduced clearances from extracellular fluid and decreased brain metabolism of the periventricular zone in iNPH resulting from glymphatic dysfunction.

Keyword

Alzheimer's disease biomarkers; idiopathic normal pressure hydrocephalus; amyloid positron-emission tomography; cerebrospinal fluid

MeSH Terms

Alzheimer Disease
Amyloid*
Biomarkers
Brain
Cerebrospinal Fluid*
Enzyme-Linked Immunosorbent Assay
Extracellular Fluid
Humans
Hydrocephalus*
Metabolism
Positron-Emission Tomography*
Amyloid
Biomarkers
Full Text Links
  • JCN
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
    DB Error: unknown error