Blood amyloid β oligomerization as a biomarker of Alzheimer’s disease: a blinded validation study

Youn, Young Chul; Lee, Byoung Sub; Kim, Gwang Je; Ryu, Ji Sun; Lim, Kuntaek; Lee, Ryan; Suh, Jeewon; Park, Young Ho; Pyun, Jung Min; Ryu, Na-Young; Kang, Min Ju; Kim, Hye Ryun; Kang, Sungmin; An, Seong Soo A.; Kim, SangYun

doi:10.21203/rs.2.19960/v1

Cited by 3 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A series of papers published recently by research consortium from Korea [75][76][77] represents the most advanced version of the prototype protocol for the detection of AβOs as a potential AD biomarker in blood using misfolded protein amplification techniques. To estimate AβO levels in blood plasma, soluble Aβ42 monomers were added ('spiked') into the aliquot of biological fluid, followed by the incubation of the mixture for 144 h. It has been shown that spiking of Aβ monomers to blood plasma samples led to an increase in AβO concentration, as measured by the increase of ThT fluorescence, when plasma sample originated from AD patient rather than normal control subject [76].…”

Section: Techniques Based On Amplification Of Misfolded Protein Conformationsmentioning

confidence: 99%

“…Recent work by Youn et al [77] reported further improvement of the AβO amplification technique. The analysis was conducted using commercially available kit (inBlood™ OAβ test), produced by People Bio Inc, Korea.…”

Section: Techniques Based On Amplification Of Misfolded Protein Conformationsmentioning

confidence: 99%

“…An "ideal" biomarker should be (1) able to detect a fundamental feature of AD neuropathology, (2) validated in neuropathologically confirmed AD cases, (3) precise (able to detect AD early in its course and distinguish it from other dementias), (4) reliable, (5) non-invasive, (6) simple to perform, (7) inexpensive. Appearance of polymeric forms of Aβ in CSF and blood is a unique feature of AD, and recent data reviewed above [73,77] indicate that analysis of AβO levels possesses a great potential for discriminating between AD and other types of neurodegenerative and neurological disorders with sufficient sensitivity and specificity. This protocol consists of two sequential steps: 1) amplification of Aβ oligomers by 'spiking' of synthetic Aβ42 monomers into a blood plasma sample, followed by incubation for 48 h; 2) application of the Multimer Detection System [75], an approach allowing to eliminate the signal from monomeric Aβ, thus detecting only Aβ oligomers.…”

Section: Amyloid-β Oligomers In Plasma: a Promising Candidate To «Ideal» Diagnostic Marker For Ad?mentioning

confidence: 99%

See 2 more Smart Citations

Development of molecular tools for diagnosis of Alzheimer’s disease that are based on detection of amyloidogenic proteins

Kulichikhin

Fedotov

Rubel

et al. 2021

Prion

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the most common form of dementia that usually occurs among older people. AD results from neuronal degeneration that leads to the cognitive impairment and death. AD is incurable, typically develops over the course of many years and is accompanied by a loss of functional autonomy, making a patient completely dependent on family members and/or healthcare workers. Critical features of AD are pathological polymerization of Aβ peptide and microtubule-associated protein tau, accompanied by alterations of their conformations and resulting in accumulation of cross-β fibrils (amyloids) in human brains. AD apparently progresses asymptomatically for years or even decades before the appearance of symptoms. Therefore, development of the early AD diagnosis at a pre-symptomatic stage is essential for potential therapies. This review is focused on current and potential molecular tools (including non-invasive methods) that are based on detection of amyloidogenic proteins and can be applicable to early diagnosis of AD. Abbreviations : Aβ – amyloid-β peptide; AβO – amyloid-β oligomers; AD – Alzheimer’s disease; ADRDA – Alzheimer’s Disease and Related Disorders Association; APH1 - anterior pharynx defective 1; APP – amyloid precursor protein; BACE1 – β-site APP-cleaving enzyme 1; BBB – brain blood barrier; CJD - Creutzfeldt-Jakob disease; CRM – certified reference material; CSF – cerebrospinal fluid; ELISA – enzyme-linked immunosorbent assay; FGD – 18 F-fluorodesoxyglucose (2-deoxy-2-[ 18 F]fluoro-D-glucose); IP-MS – immunoprecipitation-mass spectrometry assay; MCI – mild cognitive impairment; MDS – multimer detection system; MRI – magnetic resonance imaging; NIA-AA – National Institute on Ageing and Alzheimer’s Association; NINCDS – National Institute of Neurological and Communicative Disorders and Stroke; PEN2 – presenilin enhancer 2; PET – positron emission tomography; PiB – Pittsburgh Compound B; PiB-SUVR - PIB standardized uptake value ratio; PMCA – Protein Misfolding Cycling Amplification; PrP – Prion Protein; P-tau – hyperphosphorylated tau protein; RMP – reference measurement procedure; RT-QuIC - real-time quaking-induced conversion; SiMoA – single-molecule array; ThT – thioflavin T; TSEs – Transmissible Spongiform Encephslopathies; T-tau – total tau protein

show abstract

Section: Techniques Based On Amplification Of Misfolded Protein Conformationsmentioning

confidence: 99%

Section: Techniques Based On Amplification Of Misfolded Protein Conformationsmentioning

confidence: 99%

Section: Amyloid-β Oligomers In Plasma: a Promising Candidate To «Ideal» Diagnostic Marker For Ad?mentioning

confidence: 99%

See 1 more Smart Citation

Development of molecular tools for diagnosis of Alzheimer’s disease that are based on detection of amyloidogenic proteins

Kulichikhin

Fedotov

Rubel

et al. 2021

Prion

View full text Add to dashboard Cite

show abstract

“…Interestingly, 56% of these proteins were also increased in pregnant HF than SF ULF, and are involved in crucial biological events during the preimplantation period, such as energy metabolism (ACAA2, ENO1, MDH2, LOC615277, QPRT) [204,[495][496][497][498], glutathione synthesis (GSS) [499], attachment between trophectoderm and uterine LE (HSPA9) [500], de novo purine biosynthesis (ATIC) [501], amino acid metabolism (PSPH, GOT1, LAP3, WARS, AHCY) [502][503][504][505][506], and cytoskeletal organization and cell signaling (ACTN4, CAP1) [507,508].…”

Section: Discussionmentioning

confidence: 99%

Uterine regulation of preimplantation embryo development in fertility-classified heifers

Moraes¹

View full text Add to dashboard Cite

Infertility and subfertility represent pervasive problems in domestic animals and humans, and embryonic mortality is a major factor influencing reproductive efficiency. In cattle, the majority of embryonic loss occurs during the first month of gestation that involves the period of blastocyst formation, conceptus elongation, maternal recognition of pregnancy, implantation and beginning of placentation. Pregnancy success and embryonic mortality are affected by paternal, maternal, embryonic, and environmental factors, and the establishment and maintenance of pregnancy are a result of complex conceptus-endometrium interactions that results in adequate conceptuses (embryo/fetus and associated extraembryonic membranes) development, implantation and placentation. Our central hypothesis is that the uterus directly influences embryonic and conceptus development, and we proposed that heifers with consistently high or low fertility have distinct uterine capacity to support pregnancy. To test this hypothesis, serial embryo transfer (3-4 rounds) was used to classify heifers based on pregnancy success on day 28 as high fertile (HF; 100%), subfertile (SF; 25%), or infertile (IF; 0%). Next, a series of experiments were conducted using the fertility-classified heifers to investigate conceptus development and uterine biology in two time points: (1) day 14, to investigate conceptus development prior to the period when pregnancy induce changes are detected in the endometrium transcriptome; (2) at day 17, to evaluate conceptus-endometrial cross talk during the period of maternal recognition of pregnancy. Results from the studies conducted on day 14 supports the idea that: (1) circulating progesterone concentrations are not different among fertility-classified heifers; (2) conceptus development and survival by day 14 is not affected by fertility classification; (3) only minimal differences in endometrium transcriptome are detected among pregnant fertility-classified heifers. Collectively, these results indicated that the biological mechanisms underlying subfertility and infertility manifests between days 14 and 28, when pregnancy recognition signaling and conceptus elongation and implantation must occur for the establishment of pregnancy. Moreover, results from the subsequent experiments conducted at day 17 indicated that: (1) the mechanism of pregnancy loss in fertility-classified heifers start to manifest around the time of maternal recognition of pregnancy; (2) conceptus survival by day 17 is compromised in IF heifers; (3) conceptus development is advanced in HF than SF heifers; (4) conceptus transcriptome is directly influenced by the uterine environment; (5) dysregulated conceptus-endometrial interactions in SF heifers seems to be the major cause of pregnancy loss. Analysis of the uterine luminal fluid (ULF) from fertility classified heifers on day 17 established that: (1) ULF composition is affected by conceptus-endometrium interactions; (2) glucose concentrations in ULF are not different among fertility-classified heifers; (3) pregnancy induced changes in the metabolites found in ULF was diminished in SF heifers, and the majority of the metabolites that increased in the ULF of pregnant HF than SF heifers were associated with energy and amino acid metabolism; (4) increased abundance of proteins involved with energy metabolism, oxidative stress, amino acid metabolism, and cell proliferation and differentiation were detected in ULF of pregnant HF than SF heifers; (5) The lipid content of the ULF is altered by pregnancy and fertility classification; (6) overall concentrations prostaglandins and interferon tau were increased in the uterine lumen of pregnant HF than SF heifers, likely due to differences in conceptus size. Collectively, results from these studies supports the idea that the dysregulated conceptus-endometrium interactions in SF heifers affects the uterine luminal contents and impairs conceptus survival and elongation. Furthermore, knowledge gained from these studies enhances our understanding of the mechanisms regulating pregnancy loss in cattle and provides new information on uterine and conceptus biology during early pregnancy in ruminants.

show abstract

Association of Plasma Oligomerized Beta Amyloid with Neurocognitive Battery Using Korean Version of Consortium to Establish a Registry for Alzheimer’s Disease in Health Screening Population

et al. 2020

View full text Add to dashboard Cite

The increasing prevalence of Alzheimer’s disease (AD) has become a global phenomenon presenting serious social and health challenges. For detecting early molecular changes in the disease, several techniques to measure varied species of amyloid beta in the peripheral blood have been recently developed, but the efforts to associate them with cognitive assessments have yet to produce sufficient data. We prospectively collected participants from the consecutive population who visited our center for brain health screening. In total, 97 participants (F:M = 58:39) aged 69.4 ± 7.52 were assessed. Participants performed the Korean version of the Consortium to Establish a Registry for Alzheimer’s disease (CERAD-K), the clinical dementia rating (CDR), plasma oligomeric amyloid-β (OAβ) level tests, routine blood tests, ApoE genotype, and brain MRI. Among total population, 55.7% had a CDR of 0, and 40.2% had a CDR of 0.5. The results showed that word memory and word recall, and the total scores of the CERAD-K were negatively correlated with the plasma OAβ level. With a cut-off value of 0.78 ng/mL for the OAβ level and a −1.5 standard deviation of age/sex/education adjusted norms for the CERAD-K; naming, word memory, word recall, word recognition, and total score were significantly correlated with the OAβ level. No correlation between the OAβ level and mini-mental status examination was found. Our results demonstrate that the level of plasma OAβ was well correlated with the measure of cognitive function through the CERAD-K in the field data collected from consecutive populations. Studies on longitudinal comparisons with large cohorts will further validate the diagnostic value of plasma OAβ as a useful biomarker for screening AD and predicting progression.

show abstract

Blood amyloid β oligomerization as a biomarker of Alzheimer’s disease: a blinded validation study

Cited by 3 publications

References 0 publications

Development of molecular tools for diagnosis of Alzheimer’s disease that are based on detection of amyloidogenic proteins

Development of molecular tools for diagnosis of Alzheimer’s disease that are based on detection of amyloidogenic proteins

Uterine regulation of preimplantation embryo development in fertility-classified heifers

Association of Plasma Oligomerized Beta Amyloid with Neurocognitive Battery Using Korean Version of Consortium to Establish a Registry for Alzheimer’s Disease in Health Screening Population

Contact Info

Product

Resources

About