Alzheimer's disease key protein sits in brain with different structures, nature finds

Today, a study published in the journal Nature Communications reveals an interesting finding: beta-amyloid proteins used in the lab are structurally distinct from beta-amyloid proteins in the brains of patientsThis may explain why some of the panacea in the lab fails in the patient's bodythe study was led by scientists at Ulm University in GermanyIn the study, they purified beta-amyloid raw fibers from the brain tissue of the remains of three Alzheimer's patients and used cryoscope technology to analyze their structureThe results showed that the beta-amyloid fiber morphology of the three patients was different, but had a high degree of structural correlationthe structure observed under the frozen electric mirror (Photo: Source: Resources 1)interestingly, there are significant structural differences in the structure of pathogenic proteins in the patient's brain compared to beta-amyloid progenitor fibers produced through chemical synthesis or recombinant expressionFor example, samples taken in vitro tend to be left-hand-twistedThe protein in the brain is the right-hand-twisted structureIn addition, their peptidefoldfolds are significantly different than previous analysis resultsin the discussion of the paper, the authors said their discovery of the right-hand structure was "very interesting", underscoring the importance of studying real patient brain samplesHowever, the authors caution that although the observations were different, it did not mean that in vitro synthesis of beta-amyloid fibers was not necessarily disease-relatedThey conservatively point out that these findings suggest that the conditions we use to synthesize beta-amyloid progenitor fibers in vitro may be somewhat different from the real situation in the body, leading to structural differencesThe specific impact of these differences needs to be further explored"This study also helps to understand the effects of mutations caused by Alzheimer's disease on beta amyloid, or to the development of drugs that prevent the formation of these profibres,"a press release from Nature"
References: 1, Kollmer, M., Close, W., Funk, L et al Cryo-EM Structure and polymorph of Amyloid fibrils purified d'S brain tissue Nat Commun 10, 4760 (2019) doi:10.1038/s41467-019-12683-8