Systemic Inflammation and Multimodal Biomarkers in Amnestic Mild Cognitive Impairment and Alzheimer's Disease

Mol Neurobiol. 2018 Jul;55(7):5689-5697. doi: 10.1007/s12035-017-0795-9. Epub 2017 Oct 16.


There is increasing evidence suggesting that one of the most relevant pathophysiological features of Alzheimer's disease (AD) is neuroinflammation, which plays an important role in the production and regulation of AD-related proteins (amyloid beta (Aβ) and Tau) and exacerbates AD pathology. Neuroinflammation can also be induced by systemic influences (factors from outside the central nervous system). However, the role of systemic inflammation in AD pathophysiology is much less understood. Thus, our main objective in this study was to verify whether the presence of serum cytokines (IL-1β, IL-6, IL-10, IL-12, and TNF-α) affects different AD biomarkers: Aβ1-42 and Tau protein levels, hippocampal volumes (HV), and default mode network functional connectivity (DMN FC) in healthy elderly controls, amnestic mild cognitive impairment (aMCI) patients due to AD, and mild AD patients. To accomplish this, we acquired 3-T MRI, blood, and cerebrospinal fluid (CSF) samples from 42 healthy controls, 55 aMCI patients due to AD, and 33 mild AD patients. Comparing the groups, we found that the mild AD patients presented smaller HV, disrupted DMN FC, and proportionally less IL-1β than the controls. The aMCI patients only differed from the controls in DMN FC. In intra-group comparison, aMCI and mild AD with detectable levels of cytokines (TNF-α, IL-1β, IL-10, and IL-12) had decreased DMN FC. On the other hand, patients with detectable levels of IL-10 and IL-12 presented a more favorable AD biomarkers profile (larger HV, more CSF Aβ1-42, and less p-Tau), indicating a possible protective role of these ILs. Our findings indicate a possible relationship between systemic inflammation with DMN FC disruption, hippocampal atrophy, and CSF protein levels in the subjects with mild AD and aMCI.

Keywords: Alzheimer’s disease biomarkers; Cytokines; Default mode network; Functional connectivity; Hippocampal volume; Systemic inflammation.

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / complications*
  • Alzheimer Disease / diagnostic imaging
  • Biomarkers / cerebrospinal fluid*
  • Case-Control Studies
  • Cognitive Dysfunction / cerebrospinal fluid*
  • Cognitive Dysfunction / complications*
  • Cognitive Dysfunction / diagnostic imaging
  • Cytokines / cerebrospinal fluid
  • Female
  • Humans
  • Inflammation / cerebrospinal fluid*
  • Inflammation / complications*
  • Inflammation / diagnostic imaging
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests


  • Biomarkers
  • Cytokines