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

Timo Grimmer, Oliver Goldhardt, Igor Yakushev, Marion Ortner, Christian Sorg, Janine Diehl-Schmid, Hans Förstl, Alexander Kurz, Robert Perneczky, Scott Miners

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)43-50
Number of pages8
JournalNeurodegenerative Diseases
Volume19
Issue number1
Early online date2 Jul 2019
DOIs
Publication statusPublished - 1 Aug 2019

Bibliographical note

The acceptance date for this record is provisional and based upon the month of publication for the article.

Keywords

  • Alzheimer's disease
  • Amyloid clearance
  • Cerebrospinal fluid
  • CSF-Aβ
  • CSF-tau
  • FDG-PET
  • Neprilysin
  • Neuronal injury
  • Pittsburgh compound B
  • Positron emission tomography

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