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

doi:10.1159/000500811

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 journal › Article (Academic Journal) › peer-review

4 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 language	English
Pages (from-to)	43-50
Number of pages	8
Journal	Neurodegenerative Diseases
Volume	19
Issue number	1
Early online date	2 Jul 2019
DOIs	https://doi.org/10.1159/000500811
Publication status	Published - 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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10.1159/000500811

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title = "Associations of Neprilysin Activity in CSF with Biomarkers for Alzheimer's Disease",

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, Cerebrospinal fluid, CSF-Aβ, CSF-tau, FDG-PET, Neprilysin, Neuronal injury, Pittsburgh compound B, Positron emission tomography",

author = "Timo Grimmer and Oliver Goldhardt and Igor Yakushev and Marion Ortner and Christian Sorg and Janine Diehl-Schmid and Hans F{\"o}rstl and Alexander Kurz and Robert Perneczky and Scott Miners",

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Associations of Neprilysin Activity in CSF with Biomarkers for Alzheimer's Disease. / Grimmer, Timo; Goldhardt, Oliver; Yakushev, Igor; Ortner, Marion; Sorg, Christian; Diehl-Schmid, Janine; Förstl, Hans; Kurz, Alexander; Perneczky, Robert; Miners, Scott.

In: Neurodegenerative Diseases, Vol. 19, No. 1, 01.08.2019, p. 43-50.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Associations of Neprilysin Activity in CSF with Biomarkers for Alzheimer's Disease

AU - Grimmer, Timo

AU - Goldhardt, Oliver

AU - Yakushev, Igor

AU - Ortner, Marion

AU - Sorg, Christian

AU - Diehl-Schmid, Janine

AU - Förstl, Hans

AU - Kurz, Alexander

AU - Perneczky, Robert

AU - Miners, Scott

N1 - The acceptance date for this record is provisional and based upon the month of publication for the article.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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.

AB - 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.

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KW - Amyloid clearance

KW - Cerebrospinal fluid

KW - CSF-Aβ

KW - CSF-tau

KW - FDG-PET

KW - Neprilysin

KW - Neuronal injury

KW - Pittsburgh compound B

KW - Positron emission tomography

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VL - 19

SP - 43

EP - 50

JO - Neurodegenerative Diseases

JF - Neurodegenerative Diseases

SN - 1660-2862

IS - 1

ER -

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

Abstract

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