Plasma Cytokines Profile in Subjects with Alzheimer's Disease: Interleukin 1 Alpha as a Candidate for Target Therapy

Meisam Mahdavi; Saeed Karima; Shima Rajaei; Vajihe Aghamolaii; Hossein Ghahremani; Reza Ataei; Hessam Sepasi Tehrani; Somayeh Mahmoodi Baram; Abbas Tafakhori; Behnam Safarpour Lima; Somayeh Shateri; Hamid Fatemi; Farzad Mokhtari; Abdolrahim Nikzameer; Amir Yarhosseini; Ali Gorji

doi:10.31661/gmj.v10i0.1974

Plasma Cytokines Profile in Subjects with Alzheimer's Disease: Interleukin 1 Alpha as a Candidate for Target Therapy

Galen Med J. 2021 Jan 25:10:e1974. doi: 10.31661/gmj.v10i0.1974. eCollection 2021.

Authors

Meisam Mahdavi¹, Saeed Karima¹, Shima Rajaei^{1

2}, Vajihe Aghamolaii³, Hossein Ghahremani¹, Reza Ataei¹, Hessam Sepasi Tehrani², Somayeh Mahmoodi Baram^{1

2}, Abbas Tafakhori⁴, Behnam Safarpour Lima⁵, Somayeh Shateri¹, Hamid Fatemi², Farzad Mokhtari², Abdolrahim Nikzameer¹, Amir Yarhosseini³, Ali Gorji⁶

Affiliations

¹ Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran.
² Department of Clinical Research, HealthWeX Co., Ltd., ON, Canada.
³ Department of Psychiatry, School of Medicine, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Department of Neurology, School of Medicine, Iranian Center of Neurological Research, Neuroscience Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Department of Neurology, School of Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran.
⁶ Department of Neurology and Department of Neurosurgery, Westfälische Wilhelms-Universität Münster, Münster, Germany.

Abstract

Background: Alzheimer's disease (AD) is the main cause of the neurodegenerative disorder, which is not detected unless the cognitive deficits are manifested. An early prediagnostic specific biomarker preferably detectable in plasma and hence non-invasive is highly sought-after. Various hypotheses refer to AD, with amyloid-beta (Aβ) being the most studied hypothesis and inflammation being the most recent theory wherein pro-and anti-inflammatory cytokines are the main culprits.

Materials and methods: In this study, the cognitive performance of AD patients (n=39) was assessed using mini-mental state examination (MMSE), AD assessment scale-cognitive subscale (ADAS-cog), and clinical dementia rating (CDR). Their neuropsychiatric symptoms were evaluated through neuropsychiatric inventory-questionnaire (NPI-Q). Moreover, plasma levels of routine biochemical markers, pro-/anti-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-1 α (IL-1α), IL-1β, IL-2, IL-4, IL-6, IL-8, IL-12p70, IL-10, Interferon-gamma, chemokines, including prostaglandin E2 (PGE-2), monocyte chemoattractant protein-1, interferon gamma-induced protein 10, Aβ peptide species (42, 40) and Transthyretin (TTR) were measured.

Results: Our results revealed that Aβ 42/40 ratio and TTR were correlated (r=0.367, P=0.037). IL-1α was directly correlated with ADAS-cog (r=0.386, P=0.017) and Aβ 40 (r=0.379, P=0.019), but was inversely correlated with IL-4 (r=-0.406, P=0.011). Negative correlations were found between MMSE and PGE2 (r=-0.405, P=0.012) and TNF-α/ IL-10 ratio (r=-0.35, P=0.037). CDR was positively correlated with both PGE2 (r=0.358, P=0.027) and TNF-α (r=0.416, P=0.013). There was a positive correlation between NPI-caregiver distress with CDR (r=0.363, P=0.045) and ADAS-cog (r=0.449, P=0.019).

Conclusion: Based on the observed correlation between IL-1α, as a clinical moiety, and ADAS-cog, as a clinical manifestation of AD, anti-IL-1α therapy in AD could be suggested.

Keywords: Alzheimer’s Disease; Aβ Peptide; IL-1α; NPI-Q; Pro-/Anti-inflammatory Cytokines.