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

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 beta-amyloid (A beta)40, A beta 42, total tau (t-tau) protein, and phosphorylated tau (p-tau) protein in the CSF using enzyme-linked immunosorbent assays. Results The level of A beta 42 and the A beta 42/A beta 40 ratio in the CSF were significantly lower in AD than in iNPH or CN subjects. The A beta 40 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 A beta 42, A beta 40, 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 AP 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.