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

Abstract：

: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.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Magalhães TNC,Weiler M,Teixeira CVL,Hayata T,Moraes AS,Boldrini VO,Dos Santos LM,de Campos BM,de Rezende TJR,Joaquim HPG,Talib LL,Forlenza OV,Cendes F,Balthazar MLF

doi

10.1007/s12035-017-0795-9

subject

Has Abstract

pub_date

2018-07-01 00:00:00

pages

5689-5697

issue

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-017-0795-9

journal_volume

pub_type

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