Plasma Amyloid-Beta and Alzheimer’s Disease

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Alzheimer’s disease (AD) is the leading cause of memory loss or dementia. Currently, its diagnosis uses clinical criteria and the ruling out of other causes.

The clinical characteristics of Alzheimer’s disease include progressive loss of memory and impaired cognition. The impact of AD on public health includes increased rates of informal care and the direct charges of communal care (Wimo et al., 2010).

Biomarkers in AD research are useful in the prompt diagnosis of AD. It has been reported that the neurodegenerative effects of AD are irreversible. However, the associated symptoms can be addressed before they worsen. Therefore, biomarkers help in the prediction of AD.

Plasma Ab would be considered a good candidate biomarker because obtaining blood samples for the test is less invasive and more cost-effective than getting CSF samples (Gouras, Olsson, & Hansson, 2015).

The main difference between plasma and CSF Abeta is that CSF Abeta is obtained from the cerebrospinal fluid while the plasma variant is the plasma amyloid that has crossed the blood-brain barrier to the blood through special receptors such as low-density lipoprotein (Butterfield, Swomley, & Sultana, 2013).

There are no other valid measures of amyloid plaque burden because amyloid plaques arise from the deposition of Abeta 40 and 42 in the brain. These proteins can only be found in the brain, blood, and CSF.

Previous studies have shown that the concentration of Ab42 in (CSF) is diminished in patients with slight reasoning deficiency and AD. Therefore, tests that quantify CSF Ab42 as well as phospho-tau are useful in the prompt diagnosis of AD (Toledo, Shaw, & Trojanowski, 2013).

The aim of this study is to find the precise relationship between plasma amyloid beta and Alzheimer’s disease.

Methods

The nested case-control study was appropriate for the study. This approach entails the identification of a specified number of the disease under investigation. For each case, a corresponding control (without the disease at the time of the study) is selected from the same cohort. This method is reported to be effective in investigations involving biologic precursors of disease, which is the focus of this study (Keogh & Cox, 2014). Additionally, it is cheaper than full cohort studies.

The subjects were classified into dementia and dementia-free based on cognitive function tests. The subjects included males and females aged 50 and above. The study reports three measures: plasma Abeta 40, Abeta42 levels and the ratio of Abeta 42:40 in AD cases and dementia-free cases.

Means were used to depict the concentrations of plasma Abeta levels. T-tests were used to determine the differences in plasma Abeta levels between the Ad cases and dementia-free groups.

Results

The plasma Abeta 42 levels were lower in AD cases than in the controls. Similarly, plasma Abeta 40 levels were lower in AD cases than in the dementia-free group. However, the differences in the plasma Abeta levels between the AD cases and controls were not statistically significant because the P-values were greater than 0.05. The findings are summarized in Table 1.

Table 1. Association of plasma Abeta with AD.

Plasma Abeta measure AD cases Dementia-free controls Odds Ratio (95% CI) P-value
Abeta 42, mean (SD) ng/L 43.6 (13.1) 44.6 (12.5) 0.994 (0.982-1.006) 0.316
Abeta 40, mean (SD) ng/L 142.3 (36.3) 143.9 (41.0) 0.999 (0.994-1.003) 0.525
Ratio Ab42:Ab40, mean (SD) 0.325 (0.131) 0.331 (0.129) 0.664 (0.190-2.325) 0.522

Similar findings were observed in subgroup analyses according to sex (men and women) and age (<60; ≥60).

Discussion

It was observed that the plasma Abeta 40 and 42 levels were higher in cases of AD than in the dementia-free subjects. Therefore, it can be concluded that plasma Abeta levels are useful indicators of AD.

The findings of this study are in line with the current literature that Abeta levels reduce in AD (Seppälä et al., 2010).

The strength of this study is that it involved the direct comparison of plasma Abeta levels in diseased and disease-free subjects thus helping to establish a relationship between the concentrations of this proteins in AD and dementia-free states. However, the findings were not statistically significant thus introducing an element of doubt to the reliability of plasma Abeta levels in predicting the occurrence of AD.

Future studies could determine ways of optimizing the test to increase its reliability.

References

Butterfield, D. A., Swomley, A. M., & Sultana, R. (2013). Amyloid β-peptide (1–42)-induced oxidative stress in Alzheimer disease: Importance in disease pathogenesis and progression. Antioxidants & Redox Signaling, 19(8), 823-835.

Gouras, G. K., Olsson, T. T., & Hansson, O. (2015). β-amyloid peptides and amyloid plaques in Alzheimer’s disease. Neurotherapeutics, 12(1), 3-11.

Seppälä, T. T., Herukka, S. K., Hänninen, T., Tervo, S., Hallikainen, M., Soininen, H., & Pirttilä, T. (2010). Plasma Aβ42 and Aβ40 as markers of cognitive change in follow-up: A prospective, longitudinal, population-based cohort study. Journal of Neurology, Neurosurgery & Psychiatry, 81(10), 1123-1127.

Toledo, J. B., Shaw, L. M., & Trojanowski, J. Q. (2013). Plasma amyloid beta measurements: A desired but elusive Alzheimer’s disease biomarker. Alzheimer’s Research & Therapy, 5(2), 1.

Wimo, A., Jönsson, L., Bond, J., Prince, M., Winblad, B., & International, A. D. (2013). The worldwide economic impact of dementia 2010. Alzheimer’s & Dementia, 9(1), 1-11.

Keogh, R. H. & Cox, D. R. (2014). Case-control studies. Cambridge, UK: Cambridge University Press.

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