Associations of Neprilysin Activity in CSF with Biomarkers for Alzheimer's Disease

Neurodegener Dis. 2019;19(1):43-50. doi: 10.1159/000500811. Epub 2019 Jul 2.

Abstract

Background: Neprilysin (NEP) cleaves amyloid-β 1-42 (Aβ42) in the brain. Hence, we aimed to elucidate the effect of NEP on Aβ42 in cerebrospinal fluid (CSF) and on in vivo brain amyloid load using amyloid positron emission tomography (PET) with [11C]PiB (Pittsburgh compound B). In addition, associations with the biomarkers for neuronal injury, CSF-tau and FDG-PET, were investigated.

Methods: Associations were calculated using global and voxel-based (SPM8) linear regression analyses in the same cohort of 23 highly characterized Alzheimer's disease patients.

Results: CSF-NEP was significantly inversely associated with CSF-Aβ42 and positively with the extent of neuronal injury as measured by CSF-tau and FDG-PET.

Conclusions: Our results on CSF-NEP are compatible with the assumption that local degradation, amongst other mechanisms of amyloid clearance, plays a role in the development of Alzheimer's pathology. In addition, CSF-NEP is associated with the extent and the rate of neurodegeneration.

Keywords: Alzheimer’s disease; Amyloid clearance; CSF-Aβ42; CSF-tau; Cerebrospinal fluid; FDG-PET; Neprilysin; Neuronal injury; Pittsburgh compound B; Positron emission tomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / analysis*
  • Amyloid beta-Peptides / metabolism
  • Aniline Compounds
  • Apolipoprotein E4 / genetics
  • Biomarkers
  • Brain / diagnostic imaging
  • Brain Chemistry
  • Carbon Radioisotopes
  • Female
  • Fluorine Radioisotopes
  • Fluorodeoxyglucose F18
  • Humans
  • Male
  • Mental Status and Dementia Tests
  • Middle Aged
  • Neprilysin / cerebrospinal fluid*
  • Neprilysin / metabolism
  • Neuroimaging
  • Peptide Fragments / metabolism
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Thiazoles
  • tau Proteins / cerebrospinal fluid

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Apolipoprotein E4
  • Biomarkers
  • Carbon Radioisotopes
  • Carbon-11
  • Fluorine Radioisotopes
  • MAPT protein, human
  • Peptide Fragments
  • Radiopharmaceuticals
  • Thiazoles
  • amyloid beta-protein (1-42)
  • amyloid beta-protein (40-42)
  • tau Proteins
  • Fluorodeoxyglucose F18
  • Neprilysin
  • Fluorine-18