Neurodegenerative disease biomarkers Aβ 1-40, Aβ 1-42, tau, and p-tau 181 in the vervet monkey cerebrospinal fluid: Relation to normal aging, genetic influences, and cerebral amyloid angiopathy

Brain Behav. 2018 Jan 13;8(2):e00903. doi: 10.1002/brb3.903. eCollection 2018 Feb.

Abstract

Background: The Caribbean vervet monkey (Chlorocebus aethiops sabaeus) is a potentially valuable animal model of neurodegenerative disease. However, the trajectory of aging in vervets and its relationship to human disease is incompletely understood.

Methods: To characterize biomarkers associated with neurodegeneration, we measured cerebrospinal fluid (CSF) concentrations of Aβ1-40, Aβ1-42, total tau, and p-tau181 in 329 members of a multigenerational pedigree. Linkage and genome-wide association were used to elucidate a genetic contribution to these traits.

Results: 1-40 concentrations were significantly correlated with age, brain total surface area, and gray matter thickness. Levels of p-tau181 were associated with cerebral volume and brain total surface area. Among the measured analytes, only CSF Aβ1-40 was heritable. No significant linkage (LOD > 3.3) was found, though suggestive linkage was highlighted on chromosomes 4 and 12. Genome-wide association identified a suggestive locus near the chromosome 4 linkage peak.

Conclusions: Overall, these results support the vervet as a non-human primate model of amyloid-related neurodegeneration, such as Alzheimer's disease and cerebral amyloid angiopathy, and highlight Aβ1-40 and p-tau181 as potentially valuable biomarkers of these processes.

Keywords: Alzheimer's disease; amyloid beta; cerebral amyloid angiopathy; cerebrospinal fluid; tau; vervet.

Publication types

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

MeSH terms

  • Aging* / cerebrospinal fluid
  • Aging* / genetics
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides* / cerebrospinal fluid
  • Amyloid beta-Peptides* / genetics
  • Animals
  • Biomarkers / cerebrospinal fluid
  • Brain / pathology*
  • Cerebral Amyloid Angiopathy* / cerebrospinal fluid
  • Cerebral Amyloid Angiopathy* / genetics
  • Chlorocebus aethiops*
  • Chromosomes, Mammalian
  • Female
  • Genetic Linkage
  • Genome-Wide Association Study
  • Male
  • Models, Animal
  • Monkey Diseases* / cerebrospinal fluid
  • Monkey Diseases* / genetics
  • Neurodegenerative Diseases / cerebrospinal fluid
  • Neurodegenerative Diseases / genetics
  • Neuroimaging / methods
  • Organ Size
  • Pedigree
  • Peptide Fragments* / cerebrospinal fluid
  • Peptide Fragments* / genetics
  • tau Proteins* / cerebrospinal fluid
  • tau Proteins* / genetics

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • tau Proteins