Apolipoprotein E Polymorphism and Oxidative Stress in Peripheral Blood-Derived Macrophage-Mediated Amyloid-Beta Phagocytosis in Alzheimer’s Disease Patients

P. S. Jairani, P. M. Aswathy, Dhanya Krishnan, Ramsekhar N. Menon, Joe Verghese, P. S. Mathuranath, Srinivas Gopala

Research output: Contribution to journalArticle

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Abstract

Peripheral blood-derived macrophages isolated from Alzheimer’s disease (AD) patients have earlier been reported to demonstrate ineffective phagocytosis of amyloid-beta compared to the age-matched control subjects. However, the mechanisms causing unsuccessful phagocytosis remain unclear. Oxidative stress and the presence of ApoEε4 allele has been reported to play a major role in the pathogenesis of AD, but the contribution of oxidative stress and ApoEε4 in macrophage dysfunction leading to ineffective Aβ phagocytosis needs to be analyzed. Aβ phagocytosis assay has been performed using FITC-labeled Aβ and analyzed using flow cytometry and confocal imaging in patient samples and in THP-1 cells. Oxidative stress in patient-derived macrophages was analyzed by assessing the DNA damage using comet assay. ApoE polymorphism was analyzed using sequence-specific PCR and Hixson & Vernier Restriction isotyping protocol. In this study, we have analyzed the patterns of phagocytic inefficiency of macrophages in Indian population with a gradual decline in the phagocytic potential from mild cognitive impairment (MCI) to AD patients. Further, we have shown that the presence of ApoEε4 allele might also have a possible effect on the phagocytosis efficiency of the macrophages. Here, we demonstrate for the first time that oxidative stress could affect the amyloid-beta phagocytic potential of macrophages and hence by alleviating oxidative stress using curcumin, an anti-oxidant could enhance the amyloid-beta phagocytic efficacy of macrophages of patients with AD and MCI, although the responsiveness to curcumin might depends on the presence or absence of APOEε4 allele. Oxidative stress contributes significantly to decreased phagocytosis of Aβ by macrophages. Moreover, the phagocytic inefficiency of macrophages was correlated to the presence of ApoEε4 allele. This study also found that the Aβ-phagocytic potential of macrophage gets significantly enhanced in curcumin-treated patient-derived macrophages.

Original languageEnglish (US)
JournalCellular and Molecular Neurobiology
DOIs
StatePublished - Jan 1 2019

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Apolipoproteins E
Phagocytosis
Amyloid
Alzheimer Disease
Oxidative Stress
Macrophages
Apolipoprotein E4
Curcumin
Alleles
Comet Assay
Fluorescein-5-isothiocyanate
Oxidants
DNA Damage
Flow Cytometry
Polymerase Chain Reaction

Keywords

  • Alzheimer’s disease
  • Amyloid beta
  • APO E
  • Colocalization
  • Curcumin
  • Internalization
  • Macrophages
  • Mild cognitive impairment
  • Monocytes
  • Phagocytosis

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Apolipoprotein E Polymorphism and Oxidative Stress in Peripheral Blood-Derived Macrophage-Mediated Amyloid-Beta Phagocytosis in Alzheimer’s Disease Patients. / Jairani, P. S.; Aswathy, P. M.; Krishnan, Dhanya; Menon, Ramsekhar N.; Verghese, Joe; Mathuranath, P. S.; Gopala, Srinivas.

In: Cellular and Molecular Neurobiology, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Peripheral blood-derived macrophages isolated from Alzheimer’s disease (AD) patients have earlier been reported to demonstrate ineffective phagocytosis of amyloid-beta compared to the age-matched control subjects. However, the mechanisms causing unsuccessful phagocytosis remain unclear. Oxidative stress and the presence of ApoEε4 allele has been reported to play a major role in the pathogenesis of AD, but the contribution of oxidative stress and ApoEε4 in macrophage dysfunction leading to ineffective Aβ phagocytosis needs to be analyzed. Aβ phagocytosis assay has been performed using FITC-labeled Aβ and analyzed using flow cytometry and confocal imaging in patient samples and in THP-1 cells. Oxidative stress in patient-derived macrophages was analyzed by assessing the DNA damage using comet assay. ApoE polymorphism was analyzed using sequence-specific PCR and Hixson & Vernier Restriction isotyping protocol. In this study, we have analyzed the patterns of phagocytic inefficiency of macrophages in Indian population with a gradual decline in the phagocytic potential from mild cognitive impairment (MCI) to AD patients. Further, we have shown that the presence of ApoEε4 allele might also have a possible effect on the phagocytosis efficiency of the macrophages. Here, we demonstrate for the first time that oxidative stress could affect the amyloid-beta phagocytic potential of macrophages and hence by alleviating oxidative stress using curcumin, an anti-oxidant could enhance the amyloid-beta phagocytic efficacy of macrophages of patients with AD and MCI, although the responsiveness to curcumin might depends on the presence or absence of APOEε4 allele. Oxidative stress contributes significantly to decreased phagocytosis of Aβ by macrophages. Moreover, the phagocytic inefficiency of macrophages was correlated to the presence of ApoEε4 allele. This study also found that the Aβ-phagocytic potential of macrophage gets significantly enhanced in curcumin-treated patient-derived macrophages.",
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AU - Jairani, P. S.

AU - Aswathy, P. M.

AU - Krishnan, Dhanya

AU - Menon, Ramsekhar N.

AU - Verghese, Joe

AU - Mathuranath, P. S.

AU - Gopala, Srinivas

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KW - Mild cognitive impairment

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