Differential Expression of Apoptotic and Low-Grade Inflammatory Markers in Alzheimer Disease Compared to Diabetes Mellitus Type 1 and 2.

Abstract

BACKGROUND:

Neuroinflammation, impaired brain insulin signaling, and neuronal apoptosis may be interrelated in the pathophysiology of people with Alzheimer disease (AD) and diabetes, either type 1 or 2 diabetes (T1D or T2D, respectively).

METHODS:

We studied 116 patients: 41 with AD, 20 with T1D, 21 with T2D, and 34 healthy controls. The number (n) of cytokine-secreting peripheral blood mononuclear cells (PBMCs) before and after mitogenic stimulation was determined for interleukin 1β (IL1β), interleukin 6 (IL6), tumor necrosis factor (TNF) by the enzyme-linked-immuno-spot assay. Serum concentrations of C-reactive protein (CRP) and Fas ligand (FASLG) were determined by ELISA.

RESULTS:

The studied subgroups did not differ in sex but differed in age. Higher CRP concentrations were detected in the AD group than in the T1D group (P = 0.02) and lower in controls (P < 0.001). The nPBMCs was higher in AD patients after stimulation than in basal conditions: after stimulation in nTNF (P < 0.001 vs T2D; P < 0.001 vs T1D; P = 0.001 vs control), nIL6 (P = 0.039 vs T2D; P < 0.001 vs T1D; P = 0.007 vs control), and nIL1β (P = 0.03 vs control). The nPBMCs increased after stimulation with ΡΜA in all the subgroups (P < 0.001). FASLG in the AD group displayed statistically higher concentrations than in all other subgroups (P < 0.001 vs T2D; P < 0.001 vs T1D; P = 0.012 vs control). The nPBMCs was positively correlated with plasma concentrations of FASLG in the AD subgroup.

CONCLUSIONS:

Patients with AD display a low-grade systemic inflammation compared to people with diabetes. The FAS-FASLG pathway has a potential role because FASLG concentrations are positively correlated with the inflammatory response in AD. However, this positive correlation cannot be seen in people with diabetes, at least not with the apoptotic markers used in the present study.

• Authors: Krystallenia I Alexandraki, Nikolaos V Apostolopoulos, Christos Adamopoulos, Evangelia Stamouli, Georgia Dalagiorgou, Theodoros G Papaioannou, Antonios Analitis, Marianna Karamanou, Konstantinos Makrilakis, Antonios Politis, Christina Piperi
• Journal: The journal of applied laboratory medicine (J Appl Lab Med) Vol. 3 Issue 6 Pg. 1003-1013 (05 2019) ISSN: 2576-9456 [Print] England
• PMID: 31639691 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 American Association for Clinical Chemistry.

Chemical References

• Cytokines
• Fas Ligand Protein
• C-Reactive Protein

Topics

• Aged
• Alzheimer Disease (immunology)
• Apoptosis
• C-Reactive Protein (analysis)
• Correlation of Data
• Cytokines (blood)
• Diabetes Mellitus (immunology)
• Enzyme-Linked Immunospot Assay (methods)
• Fas Ligand Protein (analysis)
• Female
• Humans
• Inflammation (blood)
• Leukocytes, Mononuclear (immunology)
• Male
• Middle Aged
• Neuroimmunomodulation