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Hindawi International Journal of Alzheimer’s Disease Volume 2022, Article ID 9960832, 6 pages https://doi.org/10.1155/2022/9960832 Research Article Multimer Detection System-Oligomerized Amyloid Beta (MDS-OAβ): A Plasma-Based Biomarker Differentiates Alzheimer’s Disease from Other Etiologies of Dementia 1,2,3 1 2,4 Jacqueline Cotoong Dominguez , Jeryl Ritzi Tan Yu, Ma Fe De Guzman, 1,2,5 2 1,2,5 Encarnita Ampil , Anne Cristine Guevarra, Ma. Lourdes Joson , 2,4,6,7,8 1,3 3,9 2 Macario Reandelar Jr., Ma. Socorro Martinez, Antonio Ligsay, Ferron Ocampo, and SangYun Kim St Luke’s Medical Center, Institute for Neurosciences, Philippines Institute for Dementia Care Asia, Philippines St. Luke’s College of Medicine William H. Quasha Memorial, Philippines Research and Biotechnology Division, St. Luke’s Medical Center, Philippines Department of Neuroscience and Behavioral Medicine, Faculty of Medicine and Surgery, University of Santo Tomas, Philippines Far Eastern University, Dr. Nicanor Reyes Medical Foundation, Philippines Our Lady of Fatima University, Philippines New Era University College of Medicine, Philippines College of Science and the Graduate School, University of Santo Tomas, Philippines Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Correspondence should be addressed to Ma. Lourdes Joson; email@example.com Received 23 December 2021; Accepted 12 April 2022; Published 2 May 2022 Academic Editor: Giulia Abate Copyright © 2022 Jacqueline Cotoong Dominguez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. With emerging amyloid therapies, documentation of the patient’s amyloid status to conﬁrm the etiology of a clinical diagnosis is warranted prior to instituting amyloid-based therapy. The Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ)isa noninvasive blood-based biomarker utilized to measure Aβ oligomerization tendency. We determined the diﬀerence in MDS- OAβ ratio across the groups: (a) no cognitive impairment or subjective cognitive impairment (NCI/SCI), (b) Alzheimer’s disease (AD), (c) non-AD, and (d) mixed Alzheimer’s disease-Vascular dementia (AD-VaD). MDS-OAβ level was not signiﬁcantly diﬀerent between AD and mixed AD-VaD, but both groups were signiﬁcantly diﬀerent from the NCI/SCI and from the non-AD group. An MDS-OAβ level of >1 could potentially indicate clinical variants of AD or mixed pathology (AD-VaD). 1. Introduction cannot halt or reverse disease progression. Revisions in the diagnostic criteria of dementia due to AD based on the Alzheimer’s disease (AD) is a progressive neurodegenerative National Institute on Aging and the Alzheimer’s Association (NIA-AA) included documentation of brain amyloid via disorder that commonly aﬀects the elderly , accounting for biomarkers . Among these, the most well established and up to 80% of dementias,  with a heavy socio-economic validated are cerebrospinal ﬂuid amyloid-β 42 (Aβ ) (CSF burden [3, 4]. The diagnosis of AD at preclinical stages is crit- Aβ ) and PET amyloid imaging [5, 6]. However, these ical, because treatment after the onset of clinical symptoms 42 2 International Journal of Alzheimer’s Disease MDS-OAβ result available. Diagnosis was made at the end biomarkers are rarely utilized in the clinical setting as they are invasive and expensive and have limited accessibility to of the clinical assessment without knowing the result of the patients , leading to the development of blood-based MDS-OAβ blood test. biomarkers [8–10] which can provide minimally invasive Each eligible participant was assigned a study code, and and inexpensive methods for early screening and diagnosis data on demographic characteristics, Clinical Dementia Rat- of AD. ing (CDR) score, and etiologic diagnosis based on the clini- Brain amyloidosis is a critical hallmark of AD, and its cian’s assessment were recorded. MDS-OAβ blood test for pathologic development starts 10-20 years prior to its clinical amyloid oligomerization tendency was done as per physi- manifestation and onset of cognitive symptoms [5, 11]. There cian’s request, and the MDS-OAβ levels were obtained. is accumulating evidence that oligomerized Aβ (OAβ) is the The data collection forms were documented by a nurse clini- most neurotoxic among diﬀerent Aβ types and that aggrega- cian and reviewed by a neurologist. Data were encoded inde- tion of these oligomers is toxic in vivo . Compared to pendently, and inconsistencies were double-checked with amyloid-β plaque loads, oligomerized amyloid-β (OAβ) the data source to ensure data accuracy. was found to have higher correlation with presence and Sample size was calculated using the test of hypothesis severity of cognitive symptoms [13, 14]. Hence, Aβ oligo- for the diﬀerence between mean and standard deviation mers played a key role in pathogenesis and prediction of (SD) of MDS-OAβ among patients with MCI versus those AD diagnosis . Recently, an enzyme-linked immunosor- healthy normal control. Assuming that mean and SD of bent assay, the Multimer Detection System-Oligomeric MDS-OAß among MCI patients is 0:964 ± 0:098 and among healthy normal controls, 0:904 ± 0:130 , with an alpha Amyloid-β (MDS-OAβ), was utilized to detect Aβ oligomer- ization in plasma, correlating well with other clinical bio- error of 5%, power of 95%, and a one-tailed alternative markers such as CSF Aβ and amyloid PET . It hypothesis, sample size required is 23 per group, for a total measures the dynamic change of plasma oligomeric Aβ con- of 92 for 4 groups. centration, which is higher in AD patients compared to older adults with normal cognition . MDS-OAB had shown a 2.2. MDS-OAβ Assay Description and Procedure. The higher diagnostic accuracy in identifying AD from controls, inBlood™ oligomerized Aβ (OAβ)test (PeopleBio Inc., compared with other amyloid biomarkers that evaluates Republic of Korea) was used to quantify MDS-OAβ values plasma OAB concentrations [17–19]. However, limited stud- in the plasma from the subjects. This test is based on the ies have compared OAβ levels among individuals with AD Multimer Detection System (MDS), which is a modiﬁed enzyme-linked immunosorbent assay (ELISA) using epitope- and other dementia types [15, 17]. Given that underlying eti- ologies of cognitive decline impact emerging therapies that overlapping detection antibodies speciﬁc for the N-terminus are target-speciﬁc, clinicians need clinically valid and cost- of Aβ for the selective detection of OAβ over Aβ monomers. eﬀective biomarkers that can be utilized to provide accurate Prior to the assay, aliquots of plasma samples were diagnosis of dementia etiology. The aim of this study is to thawed at 37 C for 15 min. As indicated in the assay protocol investigate whether MDS-OAβ could assist in determination of the inBlood™ OAβ test, PBR-1 (synthetic Aβ made by of AD from dementia of other etiologies. PeopleBio Inc.) was spiked into plasma, and the mixture was incubated at 37 C for 48 hours. The incubated plasma sample mixture and serially diluted standard samples were 2. Materials and Methods added to each well of the plates. The plates were incubated 2.1. Subjects. Participants were enrolled at the Memory Cen- at about 20-25 C for 1 hour. After washing three times with ter of St. Luke’s Medical Center Global City from January washing buﬀer, W02-HRP antibody (Absolute Antibody 2018 to March 2019. All participants underwent clinical Ltd., UK) was added to the wells, and the plates were incu- evaluation and detailed neuropsychological assessment, cra- bated for 1 hour at about 20 to 25 C. To increase the sensitiv- nial magnetic resonance imaging (MRI), and MDS-OAβ ity of detection, 100 μl/well of enhanced chemiluminescence blood test (ﬁrst made available in the Philippines in Novem- substrate solution (Rockland Immunochemicals Inc., USA) ber 2017). The inclusion criteria were as follows: (1) adult was added, and the Relative Luminescence Unit (RLU) signal patients with subjective report of cognitive decline or mem- was detected using a multispectrophotometer. Dilutions pro- ory impairment; (2) diagnosed and categorized by a demen- viding signal in the linear range of the standard curves were tia specialist into one of the following: (a) no cognitive used for the conversion to RLU values to determine the con- impairment/subjective cognitive impairment (NCI/SCI): centration of oligomerized Aβ. presence of persistent cognitive symptoms without evidence of impairment in psychometric tests; (b) dementia, based on 2.3. Statistical Analysis. Data was analyzed using Statistical the DSM-IV TR criteria  and further classiﬁed into the Program for Social Sciences version 23 (SPSS Inc.: IBM). Dif- following clinical diagnosis: AD, NINCDS-ADRDA criteria ferences in patients’ clinical characteristics across diﬀerent eti- ; mixed AD-VaD, coexistence of AD and vascular demen- ological diagnosis were analyzed using Pearson Chi-square tia (VaD) as deﬁned in NINDS-AIREN criteria ; and test for categorical variables (i.e., sex, age groups, and CDR non-AD dementia, including frontotemporal dementia, severity stages), and one-way analysis of variance (ANOVA) Lewy body disease, and Parkinson dementia; (3) underwent was used for continuous variables. Two-way ANOVA was comprehensive neuropsychological assessment (clinical used to determine the diﬀerence in MDS-OAβ ratio of dementia protocol) at the Memory Service clinic; and (4) patients grouped by age and etiological diagnosis. LSD and International Journal of Alzheimer’s Disease 3 Patient recruitment 231 patients recruited Excluded: 84 incomplete evaluation or no MDS-OA𝛽 test available 147 were total sample included in the analysis Non-AD NCI/SCI AD Mixed AD/VAD dementia (N = 14) (N = 72) (N = 29) (N = 32) Figure 1: Study ﬂow-chart. Bonferroni tests were used for post hoc analysis. Signiﬁcance was only marginally signiﬁcant diﬀerence when MDS-OAβ level was set at p ≤ 0:05 (95% conﬁdence interval). patient/control (PT/C) ratio was compared across diﬀerent The conduct of this study was guided by the principles of age groups (≤59, 60-69, 70-79, and ≥80 years old) among Good Clinical Practice and in accordance with local regula- four etiologic diagnosis (p =0:07, Table 1), indicating tions and was approved by the St. Luke’s Institutional Ethics MDS-OAβ level does not signiﬁcantly vary based on age Review Committee (SL-20192). groups but more signiﬁcantly on etiologic cause of cognitive impairment and dementia. 3. Results 4. Discussion A total of 231 patients were recruited. Of these participants, 84 were excluded due to incomplete evaluation, resulting in In this study, we found that MDS-OAβ could diﬀerentiate 147 patients included in the study (Figure 1). Among those between dementias due AD versus non-AD etiologies. included, majority were females (62.6%) with a mean age Majority of the patients in this study were in the mild stage of 75:0±10:0 years (age ranged from 38 to 94 years old; with Clinical Dementia Rating (CDR) 0.5 and 1, indicating Table 1). The most prevalent clinical diagnosis was AD that MDS-OAβ could detect AD. These ﬁndings have sev- (49.0%), followed by non-AD dementia (21.8%), mixed eral implications. Given the long preclinical stage of AD, AD-VaD (19.7%), and NCI/SCI (9.5%). Clinical characteris- patients would beneﬁt from early diagnosis prior to the tics were compared across clinical diagnosis for cognitive onset of symptoms. This is consistent with results from a impairment and dementia. Results showed no signiﬁcant study by Lee et al. in which MDS-OAβ was shown to be a diﬀerence in sex distribution among the four clinical diagno- useful screening tool for individuals in the MCI stage . sis (p =0:66). On the other hand, age groups and CDR stage MDS-OAβ also had some correlation with brain volume distribution were signiﬁcantly diﬀerent across diﬀerent etio- reduction consistent with AD  and showed correlation logic diagnosis (p <0:001; Table 1). The age group distribu- with decline in memory performance , further support- tion among the NCI/SCI group was younger compared ing its utility as a noninvasive biomarker for AD. In a study among patients with AD, non-AD, and mixed AD-VaD. In by Youn et al., MDS-OAβ was able to validate the clinical terms of severity, more than half of the patients were at diagnosis of AD when compared to normal controls (sensi- the earliest stage of cognitive impairment or dementia tivity of 100% and speciﬁcity of 92.31%) . (CDR = 0:5; 57.1%), followed by mild (CDR = 1; 24.5%), The level of OAβ could provide valuable information moderate (CDR = 2; 8.2%), and severe (CDR = 3; 4.1%) with regard to the stage or AD progression. MDS-OAβ mea- dementia stages in decreasing order (Table 1). sures the oligomerization tendency of Aβ, and it was postu- The MDS-OAβ PT/C ratio was signiﬁcantly diﬀerent lated to correspond to the derivative of the sigmoid function among groups (p <0:001; Table 1). Consistently, the average of Aβ accumulation . Studies have shown that oligomer oligomerized amyloid-β (OAβ) levels were highest among concentrations were higher in MCI or early stage AD . patients with AD diagnosis, followed by mixed AD-VaD Therefore, an MDS-OAβ level of >1 in NCI/SCI subjects and lowest in the NCI/SCI group (Figure 2). Post hoc anal- can correspond to the preclinical stage of AD. As the disease ysis revealed that OAβ levels of patients with AD and mixed progresses, there is eventual attenuation in the expression of AD-VaD diagnosis were not signiﬁcantly diﬀerent from each this biomarker. Hence, low OAβ levels (<0.5) among AD other (p >0:05) but signiﬁcantly diﬀerent from patients with patients are highly suggestive of late-stage AD. A possible NCI/SCI (p <0:001) and non-AD (p <0.01) diagnosis. There explanation could be that the concentrations of biomarkers 4 International Journal of Alzheimer’s Disease Table 1: Clinical characteristics of participants. Etiologic diagnosis p value NCI/SCI (N =14)AD(N =72) Non-AD (N =32) Mixed AD-VaD (N =29) Total (N = 147) 66:07 ± 12:26 77:48 ± 7:88 71:47 ± 12:12 78:24 ± 6:94 75:08 ± 10:04 Age < 0.001 Age groups ≤59 years 6 (42.9) 1 (1.4) 6 (18.8) — 13 (8.9) 60-69 years 2 (14.3) 10 (14.1) 7 (21.9) 3 (10.3) 22 (15.1) < 0.001 70-79 years 4 (28.6) 28 (39.4) 12 (37.5) 11 (37.9) 55 (37.7) ≥80 years 2 (14.3) 32 (45.1) 7 (21.9) 15 (51.7) 56 (38.4) Sex Male 7 (50.0) 24 (33.3) 13 (40.6) 11 (37.9) 55 (37.4) 0.66 Female 7 (50.0) 48 (66.7) 19 (59.4) 18 (62.1) 92 (62.6) CDR stages Normal 9 (64.3) —— — 9 (6.1) Very mild 5 (35.7) 45 (62.5) 20 (62.5) 14 (48.3) 84 (57.1) Mild — 17 (23.6) 7 (21.9) 12 (41.4) 36 (24.5) < 0.001 Moderate — 6 (8.3) 4 (12.5) 2 (6.9) 12 (8.2) Severe — 4 (5.6) 1 (3.1) 1 (3.4) 6 (4.1) Total 14 (100.0) 72 (100.0) 32 (100.0) 29 (100.0) 147 (100.0) PT/C ratio 0:76 ± 0:32 1:22 ± 0:37 0:76 ± 0:37 1:09 ± 0:23 1:05 ± 0:40 < 0.001 PT/C ratio by age groups 0:76 ± 0:31 1:19 ± 0:00 0:65 ± 0:37 0:74 ± 0:34 ≤59 years — 0:75 ± 0:21 1:26 ± 0:57 0:89 ± 0:38 1:10 ± 0:14 1:07 ± 0:47 60-69 years 0.07 1:00 ± 0:20 1:16 ± 0:23 0:73 ± 0:40 1:19 ± 0:22 1:06 ± 0:32 70-79 years ≥80 years 0:29 ± 0:18 1:26 ± 0:41 0:79 ± 0:37 1:01 ± 0:24 1:10 ± 0:42 Data were presented as mean ± standard deviation or frequency (percentages). NCI: no cognitive impairment; SCI: subjective cognitive impairment; AD: Alzheimer’s disease; Non-AD: non-Alzheimer’s disease; Mixed AD-VaD: mixed etiology Alzheimer’s disease with either vascular cognitive impairment, subcortical ischemic vascular dementia, or cerebrovascular disease. (p > 0.05) 1.40 (p < 0.001) (p < 0.001) 1.20 1.00 (p <0.001) 0.80 0.60 (p <0.05) (p > 0.05) 0.40 NCI/SCI AD Non-AD Mixed AD/VAD Clinical diagnosis Figure 2: Comparison of the mean and 95% CI of MDS-OAβ per clinical diagnosis. Mean and 95% CI of MDS-OA International Journal of Alzheimer’s Disease 5 associated with AD pathogenesis, including OAβ, show 5. Conclusion decreasing trend after symptomatic disease progression, With the advent of emerging therapies that are targeted at denoting slowing of the neurodegenerative process . the amyloid pathology, documentation of the patient’s amy- Moreover, low levels of amyloid in AD patients could also loid status to conﬁrm etiology of clinical diagnosis is war- correspond to limbic-predominant age-related TDP-43 ranted prior to instituting amyloid-based therapy. Based on encephalopathy (LATE), which is seen in advanced elderly the current ﬁndings, MDS-OAβ is a simple, noninvasive test patients with features similar to AD. However, the underly- and could discriminate between AD and other types of neu- ing neuropathology for LATE is characterized by the pres- rodegenerative disorders. ence of TDP-43 protein inclusion bodies in the cytoplasm and accumulation of hyperphosphorylated TDP-43 in nuclei and cell processes of neurons . Lastly, patients with non- Data Availability AD dementia are expected to have low levels of OAβ; there- fore, an MDS-OAβ level of >1 in these patients could poten- The technical appendix, statistical code, and dataset used to tially indicate clinical variants of AD or mixed pathology. support the ﬁndings of this study will be made available In clinical practice, patients with cognitive decline are from the corresponding author upon request. assessed using tools such as the Mini Mental Status Exam (MMSE) and Montreal Cognitive Assessment (MoCA). Conflicts of Interest When equivocal, additional neuropsychological evaluation is often warranted . The incorporation of CSF Aβ and The authors declare no conﬂict of interest. PET amyloid biomarkers in the revised diagnostic criteria of Alzheimer’s disease (NIA-AA)  has resulted in diag- nostic and management shifts . However, amyloid imag- Acknowledgments ing biomarkers are not always a feasible option in regions where they are unavailable or unaﬀordable. In this setting, We thank the study participants for their cooperation and the underlying etiology of the dementia will best be ascer- willingness to participate. tained via a biomarker that is noninvasive, aﬀordable, and readily available with a high discriminative accuracy. References In addition to clinical diagnosis, this biomarker can also impact on the development of disease modifying therapies  S. A. Gale, D. Acar, and K. R. Daﬀner, “Dementia,” The Amer- (DMT), which aims to delay disease progression and possi- ican Journal of Medicine, vol. 131, no. 10, pp. 1161–1169, 2018. bly reverse AD [22, 29, 30]. Clinical trials of these DMTs,  M. Crous-Bou, C. Minguillón, N. Gramunt, and J. L. Moli- which include monoclonal antibodies against Aβ, such as nuevo, “Alzheimer’s disease prevention: from risk factors to aducanumab, solazenumab, and bapineuzumab, often early intervention,” Alzheimer's Research & Therapy, vol. 9, require documentation of amyloid on PET imaging on no. 1, p. 71, 2017. enrolled subjects .  C. Takizawa, P. L. Thompson, A. van Walsem, C. Faure, and Amyloid PET, which represents Aβ ﬁbrillar morphology, W. C. Maier, “Epidemiological and economic burden of Alz- and MDS-OAβ, which shows oligomerization tendency, heimer’s disease: a systematic literature review of data across reﬂect diﬀerent aspects of Aβ pathology, but in lieu of PET, Europe and the United States of America,” Journal of Alzhei- MDS-OAβ can be utilized to document amyloid pathology mer's Disease, vol. 43, no. 4, pp. 1271–1284, 2014. for which these novel interventions may be oﬀered.  Y. H. El-Hayek, R. E. Wiley, C. P. Khoury et al., “Tip of the ice- Although there has been some success in the validation berg: assessing the global socioeconomic costs of Alzheimer’s disease and related dementias and strategic implications for of plasma-based AD biomarkers, it is worth noting that stakeholders,” Journal of Alzheimer's Disease, vol. 70, no. 2, these studies were conducted in carefully selected research pp. 323–341, 2019. cohorts . The participants in this study are regular  G. M. McKhann, D. S. Knopman, H. Chertkow et al., “The patients in a memory center with a clinic-based design. diagnosis of dementia due to Alzheimer’s disease: recommen- Studies have been conducted to address the practical use of dations from the National Institute on Aging-Alzheimer’s AD biomarkers with regard to physician selection of appro- Association workgroups on diagnostic guidelines for Alzhei- priate biomarkers, eﬀective communication to patients, and mer’s disease,” Alzheimer's & Dementia, vol. 7, no. 3, decision-making of patients and caregivers . Future pp. 263–269, 2011. research can be done in the community setting as well as col-  A. Nordberg, J. O. Rinne, A. Kadir, and B. Långström, “The use laborative studies with other institutions in order to reﬂect of PET in Alzheimer disease,” Nature Reviews Neurology, more accurate numbers in regions where amyloid imaging vol. 6, no. 2, pp. 78–87, 2010. markers are unavailable or unaﬀordable. The small number  H. Hampel, S. E. O’Bryant, J. L. Molinuevo et al., “Blood-based (<14) of participants in the NCI/SCI group due to reluctance biomarkers for Alzheimer disease: mapping the road to the to testing with very minimal or no symptoms is a limitation clinic,” Nature Reviews Neurology, vol. 14, no. 11, pp. 639– that needs to be addressed in future studies. The same limi- 652, 2018. tation could be said of the mixed AD-VaD group where  S. Janelidze, E. Stomrud, S. Palmqvist et al., “Plasma β-amyloid interestingly no diﬀerence was found between this and AD in Alzheimer’s disease and vascular disease,” Scientiﬁc Reports, and the NCI/SCI groups. vol. 6, no. 1, article 26801, 2016. 6 International Journal of Alzheimer’s Disease ease,” Alzheimer's  A. Nakamura, N. Kaneko, V. L. Villemagne et al., “High per- Research & Therapy, vol. 11, no. 1, p. 40, formance plasma amyloid-β biomarkers for Alzheimer’s dis- 2019. ease,” Nature, vol. 554, no. 7691, pp. 249–254, 2018.  X. Meng, T. Li, X. Wang et al., “Association between increased  C. R. Jack, D. A. Bennett, K. Blennow et al., “NIA-AA research levels of amyloid-β oligomers in plasma and episodic memory framework: toward a biological deﬁnition of Alzheimer’s dis- loss in Alzheimer’s disease,” Alzheimer's Research & Therapy, ease,” Alzheimer's & Dementia, vol. 14, no. 4, pp. 535–562, vol. 11, no. 1, p. 89, 2019.  A. M. Fagan, C. Xiong, M. S. Jasielec et al., “Longitudinal  C. R. Jack Jr., D. S. Knopman, W. J. Jagust et al., “Tracking change in CSF biomarkers in autosomal-dominant Alzhei- pathophysiological processes in Alzheimer’s disease: an mer’s disease,” Science translational medicine, vol. 6, article updated hypothetical model of dynamic biomarkers,” Lancet 226ra230, 2014. Neurology, vol. 12, no. 2, pp. 207–216, 2013.  P. T. Nelson, D. W. Dickson, J. Q. Trojanowski et al., “Limbic-  K. L. Viola and W. L. Klein, “Amyloid β oligomers in Alzhei- predominant age-related TDP-43 encephalopathy (LATE): mer’s disease pathogenesis, treatment, and diagnosis,” Acta consensus working group report,” Brain, vol. 142, no. 6, Neuropathologica, vol. 29, no. 2, pp. 183–206, 2015. pp. 1503–1527, 2019.  C. Haass and D. J. Selkoe, “Soluble protein oligomers in neuro-  G. D. Rabinovici, C. Gatsonis, C. Apgar et al., “Association of degeneration: lessons from the Alzheimer’s amyloid β-pep- amyloid positron emission tomography with subsequent tide,” Nature reviews Molecular cell biology, vol. 8, no. 2, change in clinical management among medicare beneﬁciaries pp. 101–112, 2007. with mild cognitive impairment or dementia,” JAMA, vol. 321, no. 13, pp. 1286–1294, 2019.  R. B. Mofrad, P. Scheltens, S. Kim et al., “Plasma amyloid-β oligomerization assay as a pre-screening test for amyloid sta-  J. Cummings and N. Fox, “Deﬁning disease modifying therapy tus,” Alzheimer's Research & Therapy, vol. 13, no. 1, pp. 1– for Alzheimer’s disease,” The journal of prevention of Alzhei- 10, 2021. mer's disease, vol. 4, no. 2, pp. 109–115, 2017.  Y. C. Youn, B. S. Lee, G. J. Kim et al., “Blood amyloid-β oligo-  D. J. Selkoe and J. Hardy, “The amyloid hypothesis of Alzhei- merization as a biomarker of Alzheimer’s disease: a blinded mer’s disease at 25 years,” EMBO Molecular Medicine, vol. 8, validation study,” Journal of Alzheimer's Disease, vol. 75, no. 6, pp. 595–608, 2016. no. 2, pp. 493–499, 2020.  B. De Strooper, “Lessons from a failed γ-secretase Alzheimer  M. J. Wang, S. Yi, J. Han et al., “Oligomeric forms of amyloid-β trial,” Cell, vol. 159, no. 4, pp. 721–726, 2014. protein in plasma as a potential blood-based biomarker for  E. H. Thijssen and G. D. Rabinovici, “Rapid progress toward Alzheimer’s disease,” Alzheimer's research & therapy, vol. 9, reliable blood tests for Alzheimer disease,” JAMA Neurology, no. 1, p. 98, 2017. vol. 78, no. 2, pp. 143–145, 2021.  S. S. A. An, B. Lee, J. S. Yu et al., “Dynamic changes of oligo-  A. Wilde, I. S. Maurik, M. Kunneman et al., “Alzheimer’s bio- meric amyloid β levels in plasma induced by spiked synthetic markers in daily practice (ABIDE) project: rationale and Aβ42,” Alzheimer's Research & Therapy, vol. 9, no. 1, p. 86, design,” Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, vol. 6, no. 1, pp. 143–151, 2017.  A. N. Santos, A. Simm, V. Holthoﬀ, and G. Boehm, “A method for the detection of amyloid-β1-40, amyloid-β1-42 and amy- loid-β oligomers in blood using magnetic beads in combina- tion with ﬂow cytometry and its application in the diagnostics of Alzheimer’s disease,” Journal of Alzheimer's Dis- ease, vol. 14, no. 2, pp. 127–131, 2008.  A. Nabers, L. Perna, J. Lange et al., “Amyloid blood biomarker detects Alzheimer’s disease,” EMBO molecular medicine, vol. 10, no. 5, article e8763, 2018.  D. L. Segal, Diagnostic and Statistical Manual of Mental Disor- ders, American Psychiatric Association, 4th edition, 2000.  G. C. Roman, T. K. Tatemichi, T. Erkinjuntti et al., “Vascular dementia: diagnostic criteria for research studies: report of the NINDS-AIREN International Workshop,” Neurology, vol. 43, no. 2, pp. 250–260, 1993.  S. Hameed, J.-L. Fuh, V. Senanarong et al., “Role of ﬂuid biomarkers and PET imaging in early diagnosis and its clin- ical implication in the management of Alzheimer’s disease,” Journal of Alzheimer's disease reports, vol. 4, no. 1, pp. 21– 37, 2020.  J.-J. Lee, Y. Choi, S. Chung et al., “Association of plasma oligo- merized beta amyloid with neurocognitive battery using Korean version of consortium to establish a registry for Alzhei- mer’s disease in health screening population,” Diagnostics, vol. 10, no. 4, p. 237, 2020.  Y. C. Youn, S. Kang, J. Suh et al., “Blood amyloid-β oligomer- ization associated with neurodegeneration of Alzheimer’s dis-
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