Dement Neurocogn Disord.  2018 Jun;17(2):41-49. 10.12779/dnd.2018.17.2.41.

Plasma Oligomeric Beta Amyloid in Alzheimer's Disease with History of Agent Orange Exposure

Affiliations
  • 1Department of Neurology, Veterans Health Service Medical Center, Seoul, Korea.
  • 2Department of Bionano Technology, Gachon University, Seongnam, Korea. seongaan@gachon.ac.kr
  • 3Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam, Korea. neuroksy@snu.ac.kr

Abstract

BACKGROUND AND PURPOSE
During the Vietnam War, many Korean soldiers were exposed to Agent Orange. Until now, there existed only limited evidence of association between exposure to Agent Orange and Alzheimer's disease (AD). The main pathological feature of AD is brain amyloidosis. To explore the pathophysiological characteristic of AD with Agent Orange exposure, we compared newly developed amyloid beta (Aβ) oligomer levels in plasma between AD with Agent Orange exposure and without exposure.
METHODS
We recruited 48 AD patients with Agent Orange exposure and 66 AD patients without Agent Orange. Using the Multimer Detection System technique, which was based on an enzyme-linked immunosorbent assay, we measured Aβ oligomers in the plasma of study subjects.
RESULTS
Compared to normal control patients, plasma Aβ oligomer levels were higher in AD patients regardless of history of Agent Orange exposure. However, AD patients with Agent Orange exposure showed higher plasma Aβ oligomer levels than AD patients without Agent Orange. DISCUSSION: This study showed higher plasma Aβ oligomer levels in AD patients with Agent Orange exposure compared to AD patients without Agent Orange. This finding suggests the possibility of a different pathophysiology of AD patients with Agent Orange exposure from AD patients without Agent Orange.

Keyword

Agent Orange; Alzheimer's Disease; Plasma Aβ Oligomer

MeSH Terms

Alzheimer Disease*
Amyloid*
Amyloidosis
Brain
Citrus sinensis*
Enzyme-Linked Immunosorbent Assay
Humans
Military Personnel
Plasma*
Vietnam
Amyloid

Figure

  • Fig. 1 The MDS concept. (A) Monomers form proteins that have a single epitope that is captured by an antibody (capturing antibody: 6E10) attached to the surface of the plate. After adding a detection antibody (FF51-HRP), monomer proteins cannot be detected because the single epitope is already occupied. (B) Multimers with numerous epitopes can be detected by detection antibodies. The capturing and detection antibodies are different, but their epitopes overlap. MDS: Multimer Detection System.

  • Fig. 2 The distribution pattern of plasma Aβ oligomers determined by the MDS in the AD (AD with or without AO) and NC groups. The MDS RLU were higher in the AD without AO than the NC group (p<0.0001). The MDS RLU were higher in the AD with AO than the NC group (p<0.0001). The horizontal bar is the median MDS RLU. However, there was overlap between the 2 groups, suggesting that further optimization of the MDS is needed. Aβ: amyloid beta, MDS: Multimer Detection System, AD: Alzheimer's disease, AO: Agent Orange exposure, NC: normal control, RLU: relative luminescence units, AUC: area under the curve.

  • Fig. 3 The distribution pattern of plasma Aβ oligomers determined by the MDS in AD without AO and AD with AO groups. The MDS RLU were higher in the AD with AO than AD without AO group (p<0.0003). The horizontal bar is the median MDS RLU. However, there was overlap between the 2 groups suggesting that further optimization of the MDS is needed. Aβ: amyloid beta, MDS: Multimer Detection System, AD: Alzheimer's disease, AO: Agent Orange exposure, RLU: relative luminescence units, AUC: area under the curve.


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