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

• Kim HJ
• Lim TS
• Lee SM
• Kim TS
• Kim Y
• An YS
• Youn YC
• Park SA
• Chang J
• Moon SY

• KMID: 2451120
• DOI: http://doi.org/10.3988/jcn.2019.15.3.353

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

Figure

• 

  Fig. 1 AD biomarker levels in the cerebrospinal fluid of iNPH, AD, and CN subjects. Box plots of Aβ42 (A), Aβ40 (B), Aβ42/Aβ40 ratio (C), t-tau (D), and p-tau (E). Each box plot shows the median, first and third quartiles, and range. *p<0.05, †p<0.01 (student t-test). AD: Alzheimer's disease, iNPH: idiopathic normal-pressure hydrocephalus. Aβ: β-amyloid, AD: Alzheimer's disease, CN: cognitively normal, iNPH: idiopathic normal-pressure hydrocephalus, p-tau: phosphorylated tau, t-tau: total tau.

• 

  Fig. 2 Correlation between Aβ42 and Aβ40 levels in iNPH, AD, and CN subjects. The scatter plot shows the correlation between Aβ42 and Aβ40 levels. Representative images from an amyloid PET(+) AD scan and an amyloid PET(−) iNPH scan are shown on the right. Aβ: β-amyloid, AD: Alzheimer's disease, amyloid PET(+): amyloid positron-emission tomography-positive, amyloid PET(−): amyloid positron-emission tomography-negative, CN: cognitively normal, iNPH: idiopathic normal-pressure hydrocephalus.

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