Amyloid-β Oligomers Relate to Cognitive Decline in Alzheimer's Disease

Jongbloed, Wesley; Bruggink, Kim; Kester, Maartje I.; Visser, Pieter Jelle; Scheltens, Philip; Blankenstein, Marinus A.; Verbeek, Marcel M.; Teunissen, Charlotte E.; Veerhuis, Robert

doi:10.3233/jad-142136

Cited by 53 publications

(46 citation statements)

References 37 publications

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“…Soluble Aβ oligomer levels are related to cognitive decline in patients with AD [30]. To test whether AOE1 vaccination reduced the levels of Aβ oligomers, the mouse brain extracts were explored by Western blot analysis.…”

Section: Resultsmentioning

confidence: 99%

A vaccine with Aβ oligomer-specific mimotope attenuates cognitive deficits and brain pathologies in transgenic mice with Alzheimer’s disease

Liu

Zhang

et al. 2017

Alz Res Therapy

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Backgroundβ-Amyloid peptide (Aβ) oligomers are initial factors used to induce Alzheimer’s disease (AD) development, and Aβ monomers have normal physiological function. The antibodies or vaccines against Aβ monomers have serious problems, such as side effects and low curative effects. Therefore, it is essential to specifically target Aβ oligomers rather than monomers for the treatment of AD.MethodsThe mimotopes of Aβ oligomers were obtained by panning the phage-displayed random peptide libraries using oligomer-specific antibodies as targets and expressed on the surface of EBY100 Saccharomyces cerevisiae to generate yeast cell base vaccines. One vaccine (AOE1) induced antibodies specifically against Aβ oligomers and was selected for further study. The APP/PS1 mice were subcutaneously immunized with AOE1 eight times. The levels and characteristics of antibodies induced by AOE1 were determined by enzyme-linked immunosorbent assay. The effect of AOE1 on the cognitive deficits of AD mice was tested by novel object recognition (NOR) and Y-maze. Dot blot analysis, Western blot analysis, and immunohistochemistry were applied to measure the effects of AOE1 on Aβ pathologies, neuroinflammation, and microhemorrhages in the brains of AD mice.ResultsEight mimotope candidates of Aβ oligomers were selected and expressed on EBY100 S. cerevisiae. Only AOE1 vaccine containing mimotope L2 induced antibodies that specifically recognized Aβ42 oligomers rather than monomers. AOE1 immunization significantly increased the AD mice’s exploration times for the novel object in the NOR test and the choices for new arms in the Y-maze test, and it reduced levels of Aβ oligomers and glial activation in the AD mouse brains. No activation of Aβ-specific T cells and microhemorrhages was observed in their brains following AOE1 vaccination.ConclusionsAOE1 is the first vaccine applying the oligomer-specific mimotope as an immunogen, which could induce antibodies with high specificity to Aβ oligomers. AOE1 immunization attenuated Aβ pathologies and cognitive deficits in AD mice, decreased the overactivation of glial cells, and did not induce microhemorrhage in the brains of AD mice. These findings suggest that AOE1 may be a safer and more effective vaccine for AD treatment.

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Section: Resultsmentioning

confidence: 99%

A vaccine with Aβ oligomer-specific mimotope attenuates cognitive deficits and brain pathologies in transgenic mice with Alzheimer’s disease

Liu

Zhang

et al. 2017

Alz Res Therapy

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“…Based on epidemiological data suggesting a link between depression and AD, we hypothesized that serum Aβ oligomer levels in patients with MDD would show similar trends to plasma or serum Aβ oligomer levels in patients with AD. 19,20 In addition, a longitudinal study showed that the CSF Aβ oligomer levels decrease on an annual basis, and that this decrease is associated with cognitive decline. 18 In contrast, other studies have reported that there is no difference in CSF Aβ oligomer levels between patients with AD compared with control participants.…”

Section: Discussionmentioning

confidence: 99%

“…Several previous studies have reported higher Aβ oligomer levels in the CSF of patients with AD compared with controls, 17,18 and a negative correlation between the CSF Aβ oligomer levels and MMSE scores has also been reported. 19 It has been suggested that the reason for these contradictory results is methodological differences between the studies. 19,20 In addition, a longitudinal study showed that the CSF Aβ oligomer levels decrease on an annual basis, and that this decrease is associated with cognitive decline.…”

Section: Discussionmentioning

confidence: 99%

Serum levels and mutual correlations of amyloid β in patients with depression

Yasuda

Baba

Maeshima

et al. 2019

Geriatrics Gerontology Int

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Aim: Epidemiological studies have shown that depression is a risk factor for Alzheimer's disease (AD). Although the biological mechanism underlying the link between depression and AD is unclear, altered amyloid β (Aβ) metabolism in patients with depression has been suggested as a potential mechanism. Results from previous studies of Aβ metabolism in patients with depression have been inconsistent, and Aβ polymerization, which is a crucial process in AD pathology, has not previously been assessed.Methods: Serum levels of Aβ40, Aβ42 and Aβ oligomers were evaluated in 104 inpatients with major depressive disorder (MDD) and 132 healthy control individuals.Results: Lower serum Aβ42 levels were observed in patients with MDD, but there was no difference in serum Aβ oligomer levels between the MDD group and the healthy control group, even in older adults. Interestingly, serum Aβ oligomer levels in patients with MDD were dependent on serum Aβ42 levels, regardless of age, and this relationship was not observed in the control group.Conclusions: These results suggest that Aβ42 is more prone to aggregation and polymerization in patients with depression than in healthy individuals, suggesting a possible mechanism underlying the transition from depression to AD. Geriatr Gerontol Int 2020; 20: 125-129.

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“…Working memory and reference memory have been seriously impaired in APP/PS1 mouse model of AD (Webster et al, 2014). Injection of Aβ protein such as Aβ1-42, Aβ1-40, Aβ25-35 into the hippocampus or lateral ventricles of normal rodents also produced detrimental effects on memory formation, memory retrieval and hippocampal LTP (Borbely et al, 2014;Gordon et al, 2001;Hsiao et al, 1996;Jongbloed et al, 2014;Kervern et al, 2012;Yan et al, 2001;Zhang et al, 2009). Furthermore, a shorter fragment Aβ31-35 could induce similar detrimental effects as those of full length Aβ peptide in our previous experiments (Cheng et al, 2009;Zhang et al, 2006).…”

Section: Discussionmentioning

confidence: 99%