Abstract
ObjectiveWe assessed the performance of plasma amyloid oligomerization tendency (OAβ) as a marker for abnormal amyloid status. Additionally, we examined long-term storage effects on plasma OAβ.MethodsWe included 399 subjects regardless of clinical diagnosis from the Amsterdam Dementia Cohort and European Medical Information Framework for AD project (age, 63.8 ± 6.6; 44% female). Amyloid status was determined by visual read on positron emission tomography (PET; nabnormal = 206). Plasma OAβ was measured using the multimer detection system (MDS). Long-term storage effects on MDS-OAβ were assessed using general linear models. Associations between plasma MDS-OAβ and Aβ-PET status were assessed using logistic regression and receiver operating characteristics analyses. Correlations between plasma MDS-OAβ and CSF biomarker levels were evaluated using Pearson correlation analyses.ResultsMDS-OAβ was higher in individuals with abnormal amyloid, and it identified abnormal Aβ-PET with an area under the curve (AUC) of 0.74 (95% CI, 0.67–0.81), especially in samples with a storage duration < 4 years. Combining APOEe4 and age with plasma MDS-OAβ revealed an AUC of 81% for abnormal amyloid PET status (95% CI, 74–87%). Plasma MDS-OAβ correlated negatively with MMSE (r = − 0.29, p < .01) and CSF Aβ42 (r = − 0.20, p < 0.05) and positively with CSF Tau (r = 0.20, p = 0.01).ConclusionsPlasma MDS-OAβ combined with APOEe4 and age accurately identifies brain amyloidosis in a large Aβ-confirmed population. Using plasma MDS-OAβ as a screener reduced the costs and number of PET scans needed to screen for amyloidosis, which is relevant for clinical trials. Additionally, plasma MDS-OAβ levels appeared affected by long-term storage duration, which could be of interest for others measuring plasma Aβ biomarkers.
Highlights
Accumulating evidence shows that small soluble Amyloid-β oligomers (AβOs) are the most toxic and pathogenic form of Amyloid beta (Aβ) species in Alzheimer’s disease (AD) [1, 2]
Innotest Enzyme-linked immunosorbent assay (ELISA) were used to measure levels of cerebrospinal fluid (CSF) amyloid beta 1-42, total Total Tau (Tau) (Tau) and Tau phosphorylated at threonine 181 for 268 subjects (Fuijirebio, Ghent, Belgium)
Our results showed a correlation between plasma multimer detection system (MDS)-Amyloid oligomerization tendency (OAβ) and CSF Amyloid Beta 1-42 (Aβ42), Tau, or Mini Mental State Examination (MMSE) scores, which is in line with previous plasma Aβ monomer studies [7, 26, 27, 30]
Summary
Accumulating evidence shows that small soluble Amyloid-β oligomers (AβOs) are the most toxic and pathogenic form of Aβ species in Alzheimer’s disease (AD) [1, 2]. Many toxicities have been ascribed to AβOs including synaptic dysfunction, induction of tau pathology, neuroinflammation, impaired axonal transport, and neuronal death [3]. Proxies of Aβ plaques are measured with high sensitivity and specificity with positron emission tomography (PET) imaging or measurement of cerebrospinal fluid (CSF) Aβ42 concentrations. These methods often come with high costs or burden for the patient. Blood-based biomarkers are considered low-cost and minimally invasive alternatives
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