Abstract

BackgroundThe lack of effective treatment for Alzheimer’s disease (AD) stems mainly from the incomplete understanding of AD causes. Neuroinflammation has emerged as an important component of AD pathology, and a vast number of experimental and clinical data indicated a crucial role for the activation of the innate immune system in disease promotion and symptom progression.MethodsClinical examinations of AD patients in a different stage of disease severity in correlation with the measurement of two innate immune reactions, i.e., peripheral blood leukocyte (PBLs) resistance to viral infection (vesicular stomatitis virus, VSV) ex vivo, and cytokines: TNF-α, IFN-γ, IL-1β, and IL-10, production with enzyme-linked immunosorbent assay (ELISA), have been investigated during this preliminary study before and after 4 weeks of oral treatment with dietary supplement proline-rich polypeptide complex (PRP) (120 μg of PRP/day). The potential effect of PRP on the distribution of PBLs’ subpopulations has been specified.ResultsWe have found a deficiency in innate immune response in AD patients. It was demonstrated for the first time that the degree of PBLs resistance to VSV infection was closely related to the stage of clinical severity of AD. Our study showed significant differences in cytokine production which pointed that in AD patients innate immune mechanisms are impaired. Administration of PRP to our patients increased innate immune response of PBLs and declined pro- and anti-inflammatory cytokine production, thus subduing the excessively developed inflammatory response, especially among patients with high severity of AD. PRP did not exhibit a pro-proliferative activity. It was showed, however, significant influence of PRP on the distribution of PBLs’ subpopulations.ConclusionThe findings mentioned above might be crucial in the context of potential application of immunomodulatory therapy in AD patients and indicated PRP as a potential target for future treatments in neuroinflammatory diseases like AD.

Highlights

  • The lack of effective treatment for Alzheimer’s disease (AD) stems mainly from the incomplete understanding of AD causes

  • Cytokine production by Peripheral blood leukocytes (PBLs) differs among AD patients we examined the cytokine profile (TNF-α, Interferon gamma (IFN-γ), Interleukin 1 beta (IL-1β), and Interleukin 10 (IL-10)) produced by PBLs of AD patients with different levels of resistance/innate immunity

  • proline-rich polypeptide complex (PRP) treatment decreased cytokine production by PBLs of AD patients we investigated the effect of PRP treatment on spontaneous and vesicular stomatitis virus (VSV)-induced cytokine production by PBLs of AD patients

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Summary

Introduction

The lack of effective treatment for Alzheimer’s disease (AD) stems mainly from the incomplete understanding of AD causes. Alzheimer’s disease (AD) is the most common type of dementia that affects millions of people around the world. Age is one of the most important non-modifiable risk factor of AD; the disease primarily affects the elderly [1]. Significant feature of organismal aging is an aging of the immune system called “immunosenescence” that in consequence leads to both an impaired adaptive and innate immune response [4]. During aging of the innate immune system, inflammatory responses are dysregulated, which may lead to an exertion of proinflammatory milieu in humans. In the case of such chronic inflammation, an innate immune activation may be impaired, especially in response to pathogens [5]. The consequences of failure in the innate immune response have potential implications for age-associated chronic inflammatory conditions, including AD [6, 7]

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