MSR1 and NEP Are Correlated with Alzheimer's Disease Amyloid Pathology and Apolipoprotein Alterations

J Alzheimers Dis. 2022;86(1):283-296. doi: 10.3233/JAD-215410.

Abstract

Background: In mouse models of amyloidosis, macrophage receptor 1 (MSR1) and neprilysin (NEP) have been shown to interact to reduce amyloid burden in the brain.

Objective: The purpose of this study is to analyze these two gene products in combination with apolipoproteins and Aβ1-42 in the cerebrospinal fluid (CSF) and plasma of individuals at different stages of Alzheimer's disease (AD), as well as in autopsied brain samples from ROSMAP (Religious Orders Study and Memory and Aging Project).

Methods: CSF/plasma levels of MSR1 and NEP were measured using the sensitive primer extension assay technology. CSF Aβ1-42 was assessed with ELISA, while CSF ApoE and ApoJ were measured with the Luminex's multiplex technology. Brain MSR1, APOE, and CLU (APOJ) mRNA levels were measured with RNA-Seq and contrasted to amyloid plaques pathology using CERAD staging.

Results: While plasma and CSF MSR1 levels are significantly correlated, this correlation was not observed for NEP. In addition to be highly correlated to one another, CSF levels of both MSR1 and NEP are strongly correlated with AD status and CSF Aβ1-42, ApoE, and ApoJ levels. In the cortical tissues of subjects from ROSMAP, MSR1 mRNA levels are correlated with CLU mRNA levels and the CERAD scores but not with APOE mRNA levels.

Conclusion: The discrepancies observed between CSF/plasma levels of MSR1 and NEP with CSF Aβ1-42 and ApoE concentrations can be explained by many factors, such as the disease stage or the involvement of the blood-brain barrier breakdown that leads to the infiltration of peripheral monocytes or macrophages.

Keywords: Alzheimer’s disease; MSR1; NEP; amyloid; biomarkers; inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Amyloidogenic Proteins / metabolism
  • Amyloidosis*
  • Animals
  • Apolipoprotein E4 / genetics
  • Apolipoproteins E / metabolism
  • Biomarkers / cerebrospinal fluid
  • Carrier Proteins
  • Humans
  • Macrophages / metabolism
  • Neprilysin / genetics
  • Neprilysin / metabolism
  • Peptide Fragments / cerebrospinal fluid
  • RNA, Messenger
  • Scavenger Receptors, Class A / metabolism
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Amyloidogenic Proteins
  • Apolipoprotein E4
  • Apolipoproteins E
  • Biomarkers
  • Carrier Proteins
  • MSR1 protein, human
  • Peptide Fragments
  • RNA, Messenger
  • Scavenger Receptors, Class A
  • tau Proteins
  • Neprilysin