Abstract
Alzheimer̕s disease (AD) is a neurodegenerative disorder caused by the aggregation of the amyloid-beta peptide (Aβ), leading to amyloid plaques deposition in the brain. Although Aβaggregation pathway still remains unclear, recent studies point out the enhanced toxicity of oligomers compared to fibrils. The E4 isoform of apolipoprotein E (ApoE) is the major risk factor in AD as people carrying one ɛ4 allele have significantly higher chances to develop the disease. Nevertheless, this phenomenon is still poorly understood.Our group has shown that attenuated total reflection Fourier-transform infrared spectroscopy (ATR–FTIR) could discriminate between Aβ42 oligomers and fibrils. Indeed, oligomers display anti-parallel β-sheet spectral components while fibrils are characterized by a parallelβ-sheet organization. Using those spectral features to analyze the oligomeric content of our samples, we studied the influence of ApoE on Aβ42 aggregation. Our experiments demonstrated that ApoE3 increased the amount of Aβ42 oligomers in the sample.We can thus determine the proportion of Aβoligomers in the presence of another compound in the sample. We plan to use ATR–FTIR to assess the effects of the other isoforms of ApoE on Aβaggregation. Moreover, this could be extended to study the influence of other molecules or proteins on Aβaggregation.
Highlights
Alzheimer’s disease (AD) is the first cause of dementia worldwide
Oligomers display anti-parallel β-sheet spectral components while fibrils are characterized by a parallel β-sheet organization. Using those spectral features to analyze the oligomeric content of our samples, we studied the influence of apolipoprotein E (ApoE) on Aβ42 aggregation
We show that the more ApoE3, the more Aβ oligomers are found in the samples
Summary
Alzheimer’s disease (AD) is the first cause of dementia worldwide. Advances in medicine tend to raise life expectancy but one of the prices to pay is the increasing incidence of this age-related neurodegenerative disorder. Numerous studies are carried on to understand and cure the disease, it represents a huge challenge and a lot remains to be elucidated. The main responsible for AD is most probably the amyloid-beta peptide (Aβ), which aggregates and forms amyloid plaques in the brain. Many factors can influence the development of the disease such as age, sex, cholesterol level, obesity, Down syndrome or even brain stimulation . But so far, the presence of one or two ε4 alleles of apolipoprotein E (ApoE) represents the major known genetic risk factor in AD [9]. While E3 isoform of ApoE seems to be neutral regarding the disease, E2 carriers seem to be protected against AD. It has been reported that ApoE could influence
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