From the paper: Bee
venom phospholipase A2 ameliorates Alzheimer’s disease pathology in Aß vaccination treatment without inducing
neuro-inflammation in a 3xTg-AD mouse model (Baek et al., 2018)
Alzheimer’s disease (AD) provokes memory loss and other neurodegenerative effects in
patients and is the 6th leading cause of death in the United States
(Alzheimer’s Association, n.d.). It’s caused by the buildup of two proteins – amyloid-ß (Aß) and tau proteins – which cause nervous system
tissue to become inflamed (Alzheimer’s Association, n.d.; Baek et al., 2018).
Most current treatment options manage symptoms of the disease, but recent
research has been focused on turning to the Aß pathway as a means of slowing down or
stopping AD progression (Baek et al., 2018). There have been some attempts to
vaccinate mice against AD, but about 6% developed meningoencephalitis (Gilman et al., 2005), a
condition in which the brain and tissues become inflamed. Researchers believe
this response is caused by T cells, so they want to induce regulatory T cells
(Tregs), which work to stop T cell responses from occurring (Baek et al.,
2018). The researchers previously found that Tregs play a role in AD progression
(Baek et al., 2016) and the compound bee venom phospholipase A2 (bvPLA2) may help stop AD progression (Ye
et al., 2016). This is because bvPLA2 can promote Treg differentiation, leading
to a regression of some neurological diseases (Chung et al., 2015).
Table 1. Disease features of C57BL/6 mouse groups immunized with amyloid-ß with or without PT (Baek et al., 2018). |
The researchers also compared the Tregs and cytokines between
the different mice. In terms of Tregs, they found that the proportion of Tregs significantly
increased (from 3xTgAD levels) after vaccination (Figure 4b). There was no
significant difference between 3xTgAD/Aß, 3xTgAd/Aß+bvPLA2, and 3xTgAD/bvPLA2
groups (Figure 4b). For the cytokines, the researchers found that 3xTgAD mice had
higher levels of inflammatory cytokines than WT mice, and mice with bvPLA2 had
lower levels of some inflammatory cytokines than 3xTgAD mice (Figure 4c, 4d,
4e). The researchers also looked at the cytokine IL-10, which is produced by
Tregs (Baek et al, 2018). They found that IL-10 levels were higher in bvPLA2 mice (Figure 4f),
which suggests Tregs are induced in the bvPLA2 treatment.
Figure 4. Effects of bvPLA2 treatment on Tregs, inflammatory cytokine production, and serum anti-Aβ antibody levels in Aβ-vaccinated 3xTg-AD mice b, Percentages of CD4+CD25+Foxp3+cells. c, IL-2, d, IFN-γ, e, TNF-α, and f, IL-10 were measured using the CBA mouse T1/2/17 cytokine kit. **P < 0.01 and ***P < 0.001 vs. WT; #P < 0.05, ##P < 0.01, and ###P < 0.001 vs. 3xTgAD; ns: not significant (Baek et al., 2018). |
Furthermore, the researchers wanted to see if antibody
production is directed against Aß. They found 3xTAD mice don’t spontaneously generate
antibodies reactive to Aß. The results also indicate that bvPLA2
treatment doesn’t influence Aß-specific antibody production (Baek et al.,
2018). Additionally, the researchers looked at some neurological effects of
bvPLA2 administration. They found, among other things, that the compound enhances
glucose uptake in the brain (Baek et al., 2018). Finally, the researchers looked
at if Treg depletion affected spatial learning and memory; however, I had difficulty
understanding their findings (Baek et al., 2018).
All
in all, the data supports the hypothesis that adding bvPLA2 in the Aß vaccination may help reduce related nervous
tissue inflammation reaction. Aß vaccinated group had increased Treg
populations. Overall, the researchers found that the Tregs induced by bvPLA2
secrete IL-10, which suppress other immune cells (Baek et al., 2018). The
findings of the paper are important for AD research. Using bvPLA2 for Treg modification
may be helpful in treatment of AD. In vaccines targeting the Aß pathway, makers may have to add some bvPLA2
for immune suppression. The more we understand the Aß pathway and nervous tissue inflammation inhibition,
the closer we become to developing a cure for AD, and potentially other
neuro-degenerative diseases. In terms of further researcher, I would like to
know if the same sorts of effects occur in humans. Would humans even develop nervous
tissue inflammation as a result of a vaccine targeting the Aß pathway in the first place? If so, would
bvPLA2 help reduce it? I know vaccine trials on humans is a long way off, but I
can’t help but wonder if mice are a good model for AD-related vaccines.
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