The Relationship between Markers of Inflammation and Degeneration in the Central Nervous System and the Blood-Brain Barrier Impairment in Alzheimer's Disease

J Alzheimers Dis. 2017;59(3):903-912. doi: 10.3233/JAD-170220.

Abstract

Background: It is known that YKL-40- a marker of glial inflammation, and VILIP-1- a marker of neuronal injury, reflect functional and structural changes in AD brains, although there is limited data concerning their potential influence on blood-brain barrier (BBB) homeostasis.

Objective: Therefore, the aim of our study was to investigate the relationship between markers of inflammation and degeneration in the central nervous system (CNS) of patients with AD and mild cognitive impairment (MCI) as well as immunological response in CNS and BBB function.

Methods: Cerebrospinal fluid (CSF) concentrations of proteins tested were determined in 45 AD patients, 18 MCI subjects, and 23 non-demented controls using ELISA method.

Results: CSF concentrations of YKL-40 were significantly higher in MCI and AD patients, whereas CSF levels of VILIP-1 were statistically higher in the AD group as compared to the subjects without cognitive deficits. Elevated concentrations of YKL-40 correlated significantly with increased albumin quotient and decreased Aβ42/40 ratio in AD patients and with IgG quotient in the total study group. We did not find a relationship between VILIP-1 and immunological parameters reflecting BBB dysfunction and humoral immune response.

Conclusion: Our findings indicate that YKL-40 may contribute to decreased stability and increased permeability of BBB in AD patients. It is assumed that YKL-40 is implicated in the development of brain barriers, although its precise mechanism of action in the BBB disruption remains unrevealed. Further studies on larger groups of patients are required to confirm our hypothesis.

Keywords: Alzheimer’s disease; blood-brain barrier disruption; cerebrospinal fluid; humoral immune response in the CNS; mild cognitive impairment; neurodegeneration; neuroinflammation.

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Blood-Brain Barrier / pathology*
  • Chitinase-3-Like Protein 1 / cerebrospinal fluid*
  • Cognitive Dysfunction / cerebrospinal fluid
  • Female
  • Humans
  • Immunoglobulin G / cerebrospinal fluid
  • Male
  • Middle Aged
  • Neurocalcin / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Immunoglobulin G
  • Neurocalcin
  • VSNL1 protein, human
  • tau Proteins