Association between increased levels of amyloid-β oligomers in plasma and episodic memory loss in Alzheimer’s disease

Abstract

ObjectiveThe objectives of this study were to investigate whether the plasma levels of oligomeric amyloid-β (OAβ) were affected in Alzheimer’s disease (AD) and to examine the associations (or possible correlations) between plasma OAβ levels and memory performance.MethodThirty subjects with AD and 28 cognitively normal controls were recruited in the study. The multimer detection system (MDS) was used to measure the levels of OAβ in the plasma. In addition to assessing the general cognitive function with the Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), and Alzheimer’s Disease Assessment Scale–cognitive portion (ADAS-Cog), the common objects memory test (COMT) was used to examine the episodic memory performance. Pearson’s and partial correlation analyses were conducted to explore the associations between cognitive performance and OAβ levels in the plasma. A receiving operating curve (ROC) analysis was used to discriminate between the AD and control groups.ResultsThe plasma OAβ levels in the AD group were significantly higher than those in the control group [1.88 (0.38) ng/ml vs 1.20 (0.40) ng/ml, p < 0.001]. The elevated levels of plasma OAβ showed a strong correlation with cognitive performance in patients with AD, including an inverse correlation with scores on the MMSE (r = − 0.43, p = 0.02), CASI (r = − 0.56, p < 0.01), and the immediate recall (r = − 0.45, p = 0.01), 5-min delayed recall (r = − 0.56, p < 0.01), and 30-min delayed recall (r = − 0.71, p < 0.001) tests of the COMT, and a positive correlation with the ADAS-Cog scores (r = 0.59, p < 0.001). The EDTA plasma Aβ oligomer optical density (OD) value measured using the MDS could discriminate between the AD and control groups with an area under the curve (AUC) of 0.89. The optimal sensitivity and specificity were 82.1% and 90.0%, respectively.ConclusionThe elevated levels of OAβ in the plasma distinguished the AD and control groups and were associated with the severity of symptoms, especially memory performance, in patients with AD. Our results suggested that plasma OAβ could potentially be a simple and non-invasive blood-based biomarker for AD diagnosis. Furthermore, longitudinal studies are warranted to explore the application of plasma OAβ levels as a valid diagnostic biomarker in patients with AD.Electronic supplementary materialThe online version of this article (10.1186/s13195-019-0535-7) contains supplementary material, which is available to authorized users.

Plasma amyloid-β oligomerization assay as a pre-screening test for amyloid status

“…While techniques used in some studies, such as immunoprecipitation mass spectrometry [ 28 , 29 ], are labor-intensive and time-consuming, the Simoa assays and the MDS method allow high-throughput analysis. The MDS method highly resembles an ELISA in simplicity and automation possibilities [ 7 , 18 , 39 ] and as such, allows broad implementation. Another added value of our study is that we have tested the plasma MDS-OAβ assay in a heterogeneous cohort including other neurodegenerative or neuropsychiatric disorders besides the clinical AD spectrum, while previous plasma Aβ included primarily cohorts which contained the clinical AD spectrum (i.e., healthy controls, MCI, or AD dementia).…”

Development and Technical Validation of an Immunoassay for the Detection of APP669–711 (Aβ−3–40) in Biological Samples

“…For example, a multimer detection system employing two antibodies with overlapping N-terminal Aβ-epitopes for measuring Aβ oligomerization after spiking synthetic Aβ into blood plasma samples has been developed [ 27 ]. Correlations between the plasma oligomerized Aβ and CSF Aβ 42 , amyloid-positron-emission tomography (PET) results [ 28 ], and measures of cognitive functions [ 29 , 30 ] were reported. Other research groups discovered that the plasma ratios Aβ 42 /Aβ 40 , Aβ 1–40 /Aβ 1–42 , and APP 669–711 /Aβ 1-42 (i.e., Aβ −3–40 /Aβ 1–42 ), as measured by immunoprecipitation followed by mass spectrometry, predicted brain amyloid pathology with high accuracy [ 19 , 20 , 23 ].…”

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

“…Hwang et al [25] confirmed that the CERAD scores decreased as the disease progressed through three years of follow-up of participants in the cognitive normal, SCD, MCI, and ADD groups, and CSF Aβ42 levels in each group also decreased in correlation. In 2019, Meng et al [14] described that an increase in MDS-OAβ levels in AD patients correlated with episodic memory loss. Other studies have reported that scores on language-related evaluative tasks such as word list memory and word list recall reflect AD-associated cognitive and memory function changes [25,26].…”

“…The increase in the plasma AβO level in AD highly correlates with CSF Aβ42 and Pittsburgh compound B (PiB) PET standard uptake ratio [13]. In addition, the elevated plasma OAβ level showed a strong correlation with cognitive performance in patients with AD, including an inverse correlation with scores on the mini-mental status examination (MMSE), cognitive abilities screening instrument, the common objects memory test, and a positive correlation with the Alzheimer's disease assessment scale-cognitive portion scores [14]. The level of these biomarkers has been reported to correlate with cognitive performance, especially in patients within the mild cognitive impairment (MCI)-AD continuum, but this association is still controversial and it is unclear whether this correlation is found even in non-AD dementia.…”