Plasma Aβ Levels Research Articles

Plasma β-Amyloid Levels Associated With Structural Integrity Based on Diffusion Tensor Imaging in Subjective Cognitive Decline: The SILCODE Study.

Background: Accumulating evidence has demonstrated that plasma β-amyloid (Aβ) levels are useful biomarkers to reflect brain amyloidosis and gray matter structure, but little is known about their correlation with subclinical white matter (WM) integrity in individuals at risk of Alzheimer's disease (AD). Here, we investigated the microstructural changes in WM between subjects with low and high plasma Aβ levels among individuals with subjective cognitive decline (SCD).Methods: This study included 142 cognitively normal individuals with SCD who underwent a battery of neuropsychological tests, plasma Aβ measurements, and diffusion tensor imaging (DTI) based on the Sino Longitudinal Study on Cognitive Decline (SILCODE). Using tract-based spatial statistics (TBSS), we compared fractional anisotropy (FA), and mean diffusivity (MD) in WM between subjects with low (N = 71) and high (N = 71) plasma Aβ levels (cut-off: 761.45 pg/ml for Aβ40 and 10.74 pg/ml for Aβ42).Results: We observed significantly decreased FA and increased MD in the high Aβ40 group compared to the low Aβ40 group in various regions, including the body, the genu, and the splenium of the corpus callosum; the superior longitudinal fasciculus; the corona radiata; the thalamic radiation; the external and internal capsules; the inferior fronto-occipital fasciculus; and the sagittal stratum [p < 0.05, familywise error (FWE) corrected]. Average FA values were associated with poor performance on executive and memory assessments. No significant differences were found in either MD or FA between the low and high Aβ42 groups.Conclusion: Our results suggest that a correlation exists between WM integrity and plasma Aβ40 levels in individuals with SCD.

Plasma Biomarkers of Alzheimer's Disease in African Americans.

Background/Objective:The aim of this study was to determine if plasma concentrations of 5 surrogate markers of Alzheimer’s disease (AD) pathology and neuroinflammation are associated with disease status in African Americans.Methods:We evaluated 321 African Americans (159 AD, 162 controls) from the Florida Consortium for African-American Alzheimer’s Disease Studies (FCA3DS). Five plasma proteins reflecting AD neuropathology or inflammation (Aβ42, tau, IL6, IL10, TNFα) were tested for associations with AD, age, sex, APOE and MAPT genotypes, and for pairwise correlations.Results:Plasma tau levels were higher in AD when adjusted for biological and technical covariates. APOE ɛ4 was associated with lower plasma Aβ42 and tau levels. Older age was associated with higher plasma Aβ42, tau, and TNFα. Females had lower IL10 levels. Inflammatory proteins had strong pairwise correlations amongst themselves and with Aβ42.Conclusion:We identified effects of demographic and genetic variants on five potential plasma biomarkers in African Americans. Plasma inflammatory biomarkers and Aβ42 may reflect correlated pathologies and elevated plasma tau may be a biomarker of AD in this population.

Subjective Sleep Quality in Amnestic Mild Cognitive Impairment Elderly and Its Possible Relationship With Plasma Amyloid-β.

Study objectivesTo investigate the extent to which sleep quality associated with plasma Aβ levels in amnestic mild cognitive impairment (aMCI) elderly.MethodsA total of 172 cognitively normal (NC) elderly and 133 aMCI elderly were included in this study. For the evaluation of sleep quality, the Pittsburgh Sleep Quality Index (PSQI) was used. Levels of plasma Aβ were determined by the sandwich enzyme-linked immunosorbent assay technique. Multivariable linear regression analysis was applied to evaluate associations between sleep quality and plasma Aβ levels after adjusting potential confounders.ResultsCompared to NC subjects, participants with aMCI had a higher global PSQI score (8.72 ± 3.87 vs. 7.10 ± 3.07, p < 0.001). The global PSQI score was positively associated with plasma Aβ42 level in the aMCI group (β = 0.063, 95% CI 0.001–0.125, and p = 0.049) but not in the NC group (p > 0.05). Additionally, a higher global PSQI score was associated with a higher plasma Aβ42/Aβ40 ratio in both NC (β = 0.010, 95% CI 0.003–0.016, and p = 0.003) and aMCI groups (β = 0.012, 95% CI 0.005–0.018, and p < 0.001). The association between global PSQI score and plasma Aβ42/Aβ40 ratio was stronger in individuals with aMCI relative to the NC subjects (β = 0.076 vs. 0.030, p for interaction = 0.023).ConclusionPoor sleep quality was associated with plasma Aβ42 and Aβ42/Aβ40 ratio, with a stronger effect among individuals with aMCI. A better understanding of the role of sleep in plasma Aβ levels in aMCI patients could lead to effective sleep-based intervention against the risk of Alzheimer’s disease.

Distinct Uptake Kinetics of Alzheimer Disease Amyloid-β 40 and 42 at the Blood-Brain Barrier Endothelium.

Blood-brain barrier (BBB) endothelial cells lining the cerebral microvasculature maintain dynamic equilibrium between soluble amyloid-β (Aβ) levels in the brain and plasma. The BBB dysfunction prevalent in Alzheimer disease contributes to the dysregulation of plasma and brain Aβ and leads to the perturbation of the ratio between Aβ42 and Aβ40, the two most prevalent Aβ isoforms in patients with Alzheimer disease. We hypothesize that BBB endothelium distinguishes between Aβ40 and Aβ42, distinctly modulates their trafficking kinetics between plasma and brain, and thereby contributes to the maintenance of healthy Aβ42/Aβ40 ratios. To test this hypothesis, we investigated Aβ40 and Aβ42 trafficking kinetics in hCMEC/D3 monolayers (human BBB cell culture model) in vitro as well as in mice in vivo. Although the rates of uptake of fluorescein-labeled Aβ40 and Aβ42 (F-Aβ40 and F-Aβ42) were not significantly different on the abluminal side, the luminal uptake rate of F-Aβ42 was substantially higher than F-Aβ40. Since higher plasma Aβ levels were shown to aggravate BBB dysfunction and trigger cerebrovascular disease, we systematically investigated the dynamic interactions of luminal [125I]Aβ peptides and their trafficking kinetics at BBB using single-photon emission computed tomography/computed tomography imaging in mice. Quantitative modeling of the dynamic imaging data thus obtained showed that the rate of uptake of toxic [125I]Aβ42 and its subsequent BBB transcytosis is significantly higher than [125I]Aβ40. It is likely that the molecular mechanisms underlying these kinetic differences are differentially affected in Alzheimer and cerebrovascular diseases, impact plasma and brain levels of Aβ40 and Aβ42, engender shifts in the Aβ42/Aβ40 ratio, and unleash downstream toxic effects. SIGNIFICANCE STATEMENT: Dissecting the binding and uptake kinetics of Aβ40 and Aβ42 at the BBB endothelium will facilitate the estimation of Aβ40 versus Aβ42 exposure to the BBB endothelium and allow assessment of the risk of BBB dysfunction by monitoring Aβ42 and Aβ40 levels in plasma. This knowledge, in turn, will aid in elucidating the role of these predominant Aβ isoforms in aggravating BBB dysfunction and cerebrovascular disease.

Sleep disturbance is associated with higher plasma Aβ: A population‐based cross‐sectional study

AbstractBackgroundGrowing evidence suggest that sleep disturbance is a risk factor for Alzheimer’s disease (AD). Amyloid‐β (Aβ) deposition in the brain is a main pathophysiology of AD. Although peripheral Aβ clearance is associated with brain Aβ deposition, but the relationship between sleep disturbance and plasma Aβ levels is unclear.MethodThis was a population‐based cross‐sectional study. A total of 1459 participants from a village in the suburbs of Xi’an, China were enrolled from January 3 to March 26, 2017. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and good sleep quality defined as PSQI score&lt;5 points, poor sleep quality defined as PSQI score &gt;10. Cognitive function was assessed with the mini‐mental state examination (MMSE). Fasting venous blood was taken in the morning and plasma Aβ levels were measured by ELISA. The relationships between plasma Aβ levels and sleep quality was analyzed using multiple linear regressions.ResultAmong 1459 participants, 231 had poor sleep quality (15.83%). The log‐transformed Aβ40 level had significant difference among different sleep groups (F=3.216, p=0.040). log‐transformed Aβ40 level was higher in poor sleep quality group than that in general sleep quality group [87.17 (73.42,107.34) vs. 89.69 (74.81,125.79) pg/ml, p=0.016]. In bivariate analysis, sleep quality was negatively associated with plasma log‐transformed Aβ40 level (β=‐0.025, p=0.011).ConclusionIn the cognitively normal population, the poorer sleep quality is associated with higher plasma Aβ40 level. These indicated that sleep disturbance may relate to peripheral Aβ clearance.

Relationship between carotid atherosclerosis and plasma Aβ levels in patients with high risk of stroke

AbstractBackgroundGrowing evidence indicated that vascular factors contributed to the pathogenesis of Alzheimer’s disease (AD), but the relationship of atherosclerosis and AD is unclear. As Amyloid‐β (Aβ) deposition in the brain is a main pathophysiology of AD and plasma Aβ is closely related to Aβ deposition in the brain. In present study, we investigated the relationship between carotid atherosclerosis and plasma Aβ levels.MethodPatients with high risk of stroke were from community stroke screening in Qubao Village, Xi'an. Carotid ultrasound was used to detect carotid atherosclerosis. Venous blood was collected on an empty stomach in the morning. Plasma Aβ1‐40 and Aβ1‐42 levels were measured by ELISA. Univariate and multivariate analysis were used to investigated carotid atherosclerosis and plasma Aβ1‐40 and Aβ1‐42 levels.ResultAmong 222 participants underwent carotid ultrasound, 149 had carotid atherosclerosis (49.01%). Univariate analysis showed that plasma Aβ1‐40 level and Aβ1‐42 level had no significant differences between carotid atherosclerosis group and non‐carotid atherosclerosis group (53.15 ± 8.77 vs. 50.96 ± 8.79 pg/ml, P=0.083; 41.07 ± 6.51 vs. 39.95 ± 5.93 pg/ml, P=0.217). Multivariate linear regression analysis showed that plasma Aβ1‐40 (b=1.832, p = 0.213), plasma Aβ1‐42 (b=1.605, P=0.131) and plasma Aβ1‐40/Aβ1‐42 ratio (b=‐0.012, P = 0.829) had no significant difference between two groups in the total population. However, in the non‐hypertensive population, plasma Aβ1‐40 and Aβ1‐42 were significantly higher in the carotid atherosclerosis group than those in the non‐carotid atherosclerosis group (b=6.774, 95% CI: 2.691‐10.858 pg/ml, P =0.001; b=3.408, 95% CI: 0.309‐6.508 pg/ml, P=0.032).ConclusionAmong patients with high risk of stroke, carotid atherosclerosis was associated with higher plasma Aβ levels in non‐hypertension group. These indicated that atherosclerosis may be related to AD, and the relationships may be confounded by hypertension.

Plasma amyloid‐β dynamics are regulated by the sleep‐wake cycle

AbstractBackgroundIt has been reported that sleep is an important physiological process and conducive to the elimination of brain metabolites and the recovery of brain function. Growing evidence suggested that sleep disorders were related to increased risk of AD and Aβ accumulation in the brain. Although peripheral Aβ clearance is associated with brain Aβ deposition, but the relationship between sleep‐wake cycle and plasma Aβ levels is unclear.MethodThirty cognitively normal healthy adults (aged 29.07 ± 8.12), sixteen males (53.33%), were recruited. Participants underwent normal sleep and peripheral blood samples were collected every three hours between 20:00 and 8:00 the next day. Plasma Aβ40, Aβ42, total tau, phosphorylated tau 181 (P‐tau), soluble low‐density lipoprotein receptor‐related protein (sLRP1) and soluble receptors for advanced glycation end products (sRAGE) levels were measured using ELISA kits.ResultPlasma Aβ40 concentration at 5:00 decreased significantly compared with plasma level at 23:00 (p=0.041), and there is a dynamic tendency of decreasing after sleep onset and increasing after awake, which is in accordance with the sleep‐wake cycle. Furthermore, Aβ40 and Aβ42 levels were positively correlated with plasma sLRP1 (Aβ40: r=0.1791, p=0.0283; Aβ42: r=0.1780, p=0.0293). However, there was no significant dynamic change in Aβ42, Tau, P‐tau, Tau, sLRP1 and sRAGE levels in twelve hours.ConclusionPlasma Aβ40 dynamics are regulated by the sleep‐wake cycle, and it may play a positive feedback regulating role in sLRP1 level.

Metabolic syndrome is associated with plasma β‐amyloid levels in ApoE ε4 non‐carriers

AbstractBackgroundThe relationship between metabolic syndrome (MetS) and Alzheimer’s disease (AD) is not fully understood. As Amyloid‐β (Aβ) deposition in the brain is a main pathophysiology of AD and plasma Aβ is closely related to Aβ deposition in the brain, in present study, we investigated the relationship between plasma Aβ and MetS in community population.MethodThis was a population‐based cross‐sectional study. A total of 1275 participants from a village in the suburbs of Xi’an, China were enrolled from October 2014 to March 2015. Fasting venous blood was taken in the morning and plasma Aβ levels were measured by ELISA. The ApoE genotype was detected using polymerase chain reaction and Sanger sequencing. Metabolic syndrome was diagnosed according to ATP‐III riteria, and MetS severity z scores (MetS‐Z) were calculated from waist circumference, triglycerides, HDL cholesterol, systolic blood pressure, and fasting glucose. Relationships between plasma Aβ and MetS were determined using multiple linear regressions.ResultIn the total population and the ApoE ε4 non‐carriers, MetS was associated with higher plasma Aβ40 level (51.704±8.594 pg/ml vs. 53.536±8.063pg/ml, p=0.002;51.693±8.626 pg/ml vs. 53.593±7.990 pg/ml, p=0.003) and lower Aβ42/ Aβ40 ratio(0.814±0.189 vs 0.784±0.170, p=0.018;0.813±0.189 vs. 0.778±0.172, p=0.011). In the multivariable regression analysis, plasma Aβ40 was associated with MetS in the total population and ApoE ε4 non‐carriers (β=1.711, p=0.008; β=1.661, p=0.019) and Aβ42/ Aβ40 ratio (β=‐0.031, p=0.030; β=‐0.035, p=0.024). Furthermore, plasma Aβ40 correlated positively with MetS‐Z in the total population (r=0.073, p=0.009) and the ApoE ε4 non‐carriers (r=0.074, p=0.015), while Aβ42/Aβ40 ratio was negatively related with MetS (r=‐0.064, p=0.038) in ApoE ε4 non‐carriers, but not in ApoE ε4 carriers. There was no significant correlation between MetS and plasma Aβ42.ConclusionMetabolic syndrome was associated with higher plasma Aβ40 level and lower Aβ42/ Aβ40 ratio in ApoE ε4 non‐carriers, but not in ApoE ε4 carriers. This indicated that the relationships between MetS and plasma Aβ may be confounded by ApoE ε4 status.

ACI‐24 vaccine in adults with Down syndrome

AbstractBackgroundIndividuals with Down syndrome (DS) are at increased risk for developing Alzheimer’s Disease (AD) with 100% exhibiting amyloid pathology by age 40, making approaches targeting beta‐amyloid a rational strategy for the prevention of dementia. ACI‐24 is a liposomal vaccine eliciting polyclonal anti‐Aβ antibodies in a T‐cell independent manner. In this study, the safety, tolerability and immunogenicity of ACI‐24 in adults with DS are being tested.MethodsThis is a sequential, dose‐escalating, placebo‐controlled, phase 1b study testing the safety and efficacy of ACI‐24 in two cohorts with 8 individuals each. Cohort 1 (ACI‐24 300μg or placebo) was followed by cohort 2 (ACI‐24 1000μg or placebo) each comprised of 6 active and 2 placebo‐treated participants. Each participant received 7 subcutaneous injections of ACI‐24 or placebo over 12 months, followed by a 12‐month safety follow‐up period. Participants are non‐demented DS individuals (25 to 45 yrs), able to complete study‐related procedures with a reliable study partner. Primary endpoints assess the safety and tolerability, including adverse events and other safety measures as well as the induction of anti‐Aβ antibody titers in serum. Secondary objectives explore the effect of ACI‐24 on cognition and behavior (Brief Praxis Test, Clinical Global Impression of Change, Vineland II Adaptive Behavior Scale, Neuropsychiatric Inventory and selected measures of the CANTAB), standard AD biomarkers, including Aβ and tau levels in plasma and/or CSF when available; T‐cell activation; and the effect on whole brain, ventricular and hippocampal volumes.ResultsSixteen participants were randomized into two study cohorts: cohort 1 (n=8; mean age 34.1 yrs) and cohort 2, (n=8, mean age 31.1 yrs). The majority of participants are Caucasian. The study population also has a high prevalence of obesity (mean BMI = 39.6). The safety and tolerability have been good to date, with no reported dropouts, serious adverse events or MRI abnormalities.ConclusionThe recruitment of this world’s first clinical study using an anti‐Aβ vaccine (ACI‐24) in a DS population is now complete and has shown a good safety and tolerability to date. It represents a critical advance in developing potential therapies for the prevention of AD dementia in this at‐risk population.

Decreased plasma Aβ levels were not associated with post‐stroke cognitive impairment

AbstractBackgroundIt has been reported that stroke promotes the deposition of Aβ in the brain, which may be associated with post‐stroke cognitive impairment. Considering plasma Aβ is closely related to Aβ deposition in the brain, in the present study, we investigated the relationship between plasma Aβ levels and cognitive dysfunction after stroke.MethodA total of 138 patients of acute ischemic stroke (within 2 weeks of onset) who were hospitalized in the Neurology Department of the first affiliated hospital of Xi 'an Jiaotong University and 138 age‐matched controls were enrolled between Jan1, 2017, and Oct 30, 2018. The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) was used to assess the pre‐existing cognitive status. A validated Chinese version of the Mini‐Mental State Examination was used to assess cognition. Fasting venous blood was taken in the morning and plasma Aβ42, Aβ40, sLRP1, and sRAGE levels were measured by ELISA. The relationship between plasma Aβ and cognitive impairment was analyzed using logistic regression analysis.ResultAmong acute ischemic stroke 138 patients, 37 patients met the criteria for cognitive impairment, the incidence of cognitive impairment was 26.81%. Plasma Aβ42, sLRP‐1 and Aβ42/Aβ40 ratio were decreased in the acute ischemic stroke group. While plasma Aβ40, Aβ42, sLRP‐1, sRAGE levels and Aβ42/Aβ40 ratio had no significant difference between cognitive impairment group and the normal cognitive group. The multivariate analysis showed that plasma Aβ40, Aβ42, sLRP‐1, sRAGE levels and Aβ42/Aβ40 ratio were not associated with post‐stroke cognitive impairment.ConclusionPlasma Aβ42, sLRP‐1 and Aβ42/Aβ40 ratio were decreased after acute ischemic stroke, however, the levels of plasma Aβ and transports were not associated with post‐stroke cognitive impairment.

Comparison of ELISA- and SIMOA-based quantification of plasma A\u03b2 ratios for early detection of cerebral amyloidosis

BackgroundBlood-based amyloid biomarkers may provide a non-invasive, cost-effective and scalable manner for detecting cerebral amyloidosis in early disease stages.MethodsIn this prospective cross-sectional study, we quantified plasma Aβ1–42/Aβ1–40 ratios with both routinely available ELISAs and novel SIMOA Amyblood assays, and provided a head-to-head comparison of their performances to detect cerebral amyloidosis in a nondemented elderly cohort (n = 199). Participants were stratified according to amyloid-PET status, and the performance of plasma Aβ1–42/Aβ1–40 to detect cerebral amyloidosis was assessed using receiver operating characteristic analysis. We additionally investigated the correlations of plasma Aβ ratios with amyloid-PET and CSF Alzheimer’s disease biomarkers, as well as platform agreement using Passing-Bablok regression and Bland-Altman analysis for both Aβ isoforms.ResultsELISA and SIMOA plasma Aβ1–42/Aβ1–40 detected cerebral amyloidosis with identical accuracy (ELISA: area under curve (AUC) 0.78, 95% CI 0.72–0.84; SIMOA: AUC 0.79, 95% CI 0.73–0.85), and both increased the performance of a basic demographic model including only age and APOE-ε4 genotype (p ≤ 0.02). ELISA and SIMOA had positive predictive values of respectively 41% and 36% in cognitively normal elderly and negative predictive values all exceeding 88%. Plasma Aβ1–42/Aβ1–40 correlated similarly with amyloid-PET for both platforms (Spearman ρ = − 0.32, p < 0.0001), yet correlations with CSF Aβ1–42/t-tau were stronger for ELISA (ρ = 0.41, p = 0.002) than for SIMOA (ρ = 0.29, p = 0.03). Plasma Aβ levels demonstrated poor agreement between ELISA and SIMOA with concentrations of both Aβ1–42 and Aβ1–40 measured by SIMOA consistently underestimating those measured by ELISA.ConclusionsELISA and SIMOA demonstrated equivalent performances in detecting cerebral amyloidosis through plasma Aβ1–42/Aβ1–40, both with high negative predictive values, making them equally suitable non-invasive prescreening tools for clinical trials by reducing the number of necessary PET scans for clinical trial recruitment.Trial registrationEudraCT 2009-014475-45 (registered on 23 Sept 2009) and EudraCT 2013-004671-12 (registered on 20 May 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004671-12/BE).

Cross-Sectional and Longitudinal Associations Between Plasma Neurodegenerative Biomarkers and Physical Performance Among Community-Dwelling Older Adults

Abstract Background Plasma amyloid-beta (Aβ), neurofilament light chain (NfL), and progranulin (PGRN) have been related to multiple neurodegenerative conditions that might affect physical performance. The aim of this study was to explore the relationship between these plasma neurodegenerative markers and physical performance among community-dwelling older adults. Methods Five hundred and seven older adults (aged 76 ± 5 years) previously recruited in the Multidomain Alzheimer’s Preventive Trial, and had received blood and physical performance tests, were included in this study. Plasma Aβ (Aβ 42/Aβ 40 ratio), NfL, and PGRN levels were measured. Physical performance was assessed by handgrip strength and the Short Physical Performance Battery (combining gait speed, chair stands, and balance tests). Physical performance measured at the same time point and after the blood tests were used. Mixed-effect linear models were performed with age, sex, allocation to Multidomain Alzheimer’s Preventive Trial group, body mass index, and Mini-Mental State Examination score as covariates. Results The mean values of Aβ 42/Aβ 40 ratio, NfL, and PGRN were 0.11, 84.06 pg/mL, and 45.43 ng/mL, respectively. At the cross-sectional level, higher plasma NfL was associated with a lower Short Physical Performance Battery score (β = −0.004, 95% CI [−0.007, −0.001]). At the longitudinal level, higher PGRN levels were associated with decreasing handgrip strength over time (β = −0.02, 95% CI [−0.04, −0.007]). All the other associations were statistically nonsignificant. Conclusion Our findings suggest the possibility of using plasma NfL and PGRN as markers of physical performance in older adults.

Clinical value of amyloid-beta1-40 as a marker of thrombo-inflammation in antiphospholipid syndrome.

Amyloid-beta1-40 (Aβ40) is a pro-inflammatory peptide under investigation as a novel biomarker of vascular inflammation, endothelial dysfunction and atherothrombosis in the general population. Herein we tested the hypothesis that Aβ40 is deregulated in APS, a systemic autoimmune disease characterized by a thrombo-inflammatory state. Between January 2016 and July 2017, we consecutively recruited 80 regularly followed thrombotic APS patients (44 primary, 36 SLE/APS) and 80 age- and sex-matched controls. Plasma Aβ40 levels were measured using ELISA and APS-related clinical and laboratory characteristics were recorded. The adjusted Global Anti-Phospholipid Syndrome Score (aGAPSS), a validated risk score in APS, was calculated as a comparator to Aβ40 performance to detect arterial thrombotic APS-related events. Higher Aβ40 levels were significantly associated with the presence of APS [odds ratio (OR) 1.024 per 1 pg/ml (95% CI 1.007, 1.041)] after adjustment for cardiovascular risk factors (CVRFs), including smoking, arterial hypertension, dyslipidaemia and BMI, and for estimated glomerular filtration rate (eGFR). Among APS patients, increased high-sensitivity CRP (hs-CRP) serum levels was the only independent determinant of Aβ40 levels. Importantly, Aβ40 levels above the optimal receiver operating characteristics (ROC)-derived cut-off value were independently associated with recurrent arterial events [OR 4.93 (95% CI 1.31, 18.51)] after adjustment for age, sex, CVRFs, hs-CRP and high anti-β2 glycoprotein I IgG titres. Finally, by ROC curve analysis, Aβ40 provided incremental additive value over the aGAPSS by significantly improving its discrimination ability for recurrent arterial thromboses. In APS, Aβ40 plasma levels are elevated and associated with an adverse thrombo-inflammatory profile. The pathophysiological and prognostic role of Aβ40 in APS merits further investigation.

Higher Plasma Amyloid-β Levels Are Associated with a Higher Risk of Cancer: A Population-Based Prospective Cohort Study

Various studies show an inverse relation between Alzheimer disease and cancer, but findings are likely to be biased by surveillance and survival bias. Plasma amyloid-β (Aβ) is defined as a preclinical feature of Alzheimer disease, with lower levels of Aβ42 being associated with a higher risk of Alzheimer disease. To get more insight into the biological link between Alzheimer disease and cancer, we investigated plasma Aβ levels in relation to the risk of cancer. Between 2002 and 2005, we measured plasma Aβ40 and Aβ42 levels in 3,949 participants from the population-based Rotterdam Study. These participants were followed until the onset of cancer, all-cause dementia, death, loss to follow-up, or January 1, 2014, whichever came first. We used Cox proportional hazards models to investigate the association between plasma Aβ40 and Aβ42 levels, and the risk of cancer. Analyses were stratified by cancer site. During a median (interquartile range) follow-up of 9.0 years (6.9-10.1), 560 participants were diagnosed with cancer. Higher levels of log2 plasma Aβ40 and Aβ42 were associated with a higher risk of cancer [hazard ratio per standard deviation increase for Aβ40 = 1.12 (95% confidence interval, CI = 1.02-1.23) and Aβ42 = 1.12 (95% CI = 1.03-1.23)]. These effect estimates were most pronounced for hematologic cancers, urinary tract cancers, and cancers of unknown primary origin. We found that higher levels of both plasma Aβ40 and Aβ42 were associated with a higher risk of cancer. Our study suggests a potential biological link between Alzheimer disease and cancer. The pathophysiologic role of Aβ in cancer and its causality warrant further investigation.

Non-linear Relationship Between Plasma Amyloid-β 40 Level and Cognitive Decline in a Cognitively Normal Population

ObjectivesRecent studies regarding the relationships between plasma amyloid-β (Aβ) levels and cognitive performance had inconsistent results. In this study, we aimed to characterize the relationship between cognitive decline and plasma Aβ levels in a large-sample cognitively normal population.MethodsThis population-based, prospective cohort study included 1,240 participants with normal cognition. The Mini-Mental State Examination (MMSE) was used to assess cognitive function at baseline and 2 years later. Restricted cubic splines, multivariate logistic regression, and multivariate linear regression models were used to evaluate the type of relationship between cognitive decline during the 2-year follow-up period and plasma Aβ levels (Aβ40, Aβ42, and Aβ42/40).ResultsParticipants with moderate Aβ40 levels had the highest risk of cognitive decline during a 2-year follow-up relative to individuals with low Aβ40 [odds ratio (OR): 0.60, 95% confidence interval (CI): 0.45–0.81, p < 0.001] or high Aβ40 (OR: 0.65, 95% CI: 0.49–0.87, p = 0.004) levels. The association between Aβ40 and cognitive decline did not depend on sex, education level, or APOE ε4 status. There was an interaction found between age (≤ 65 and > 65 years) and Aβ40 (p for interaction = 0.021). In individuals older than 65 years, there was a positive linear relationship between plasma Aβ40 and cognitive decline (OR: 1.02, 95% CI: 1.00–1.04, p = 0.027). For participants ≤ 65 years old, the lower Aβ40 and higher Aβ40 groups had a lower risk of cognitive decline than the medium Aβ40 group (OR: 0.69, 95% CI: 0.50–0.94, p = 0.02; OR: 0.63, 95% CI: 0.45–0.86, p = 0.004). None of relationship between plasma Aβ42, Aβ42/40 and cognitive decline was found during a 2-year follow-up.ConclusionThe relationship between plasma Aβ40 and cognitive decline was not linear, but an inverted-U shape in a cognitively normal population. The underlying mechanism requires further investigation.

Detection of cognitive decline in metabolic syndrome

Abstract Background Metabolic syndrome (MetS), a risk factor for many vascular conditions, may be a prodromal manifestation of vascular cognitive impairment. Diagnosing early stages of cerebrovascular pathology can lead to prevention and delay of the progression of pathological conditions such as vascular cognitive impairment. Methods The objective of the study was to investigate new biomarkers for early diagnosis of MetS and cognitive decline as a follow-up. A cardiological, neuropsychological and neurological study was conducted among 75 Bulgarian participants. Beta amyloid in the blood, procalcitonin (PCT), NT-proBNP as predictors of cognitive impairment in patients with metabolic syndrome were identified. Clinical, anthropometric, biochemical, neuropsychological, cognitive and statistical data processing. Plasma amyloid beta (Aβ) levels, procalcitonin, NT-proBNP in MetS were investigated in participants with MetS and in group of healthy people. Results In the present study, plasma levels of Aβ42 and Aβ40 were found to be reduced in MetS participants. Procalcitonin concentration was significantly higher in males than in females. NT-proBNP was significantly higher in females than in males (p &amp;lt; 0.001). Regression analysis showed a positive relationship between NT-proBNP and systolic blood pressure (p &amp;lt; 0.001) and fasting blood glucose (p &amp;lt; 0.05). An inverse relation between NT-proBNP and diastolic blood pressure, waist circumference, triglycerides, HDL- and LDL cholesterol was found. Conclusions There was a positive association between PCT levels, decreased levels of Aβ42 and Aβ40, as well as elevated NT-proBNP and cognitive impairment in people with MetC. A concentration of NT-proBNP of 60 pg / ml or greater could be an indicator of metabolic abnormalities and early cognitive decline. Key messages Metabolic syndrome may be a prodromal manifestation of vascular cognitive impairment. The use of new biomarkers for diagnosis can lead to preventing and slowing the progression of complications associated with MetS.

Effect of Times to Blood Processing on the Stability of Blood Proteins Associated with Dementia

Background: The stability of proteins in the collecting tubes after blood draw is critical to the measured concentrations of the proteins. Although the guidelines issued by the Clinical and Laboratory Standards Institute (CLSI) suggest centrifugation should take place within 2 h of drawing blood, it is very difficult to follow these guidelines in hospitals or clinics. It is necessary to study the effect of times to blood processing on the stability of the proteins of interest. Methods: In this work, the plasma proteins of interest were those relevant to dementia, such as amyloid β 1–40 (Aβ_1–40), Aβ_1–42, Tau protein (Tau), and α-synuclein. The times to blood processing after blood draw ranged from 0.5 to 8 h. The storage temperatures of blood were room temperature (approx. 25°C) and 30°C. After storage, blood samples were centrifuged at room temperature to obtain plasma samples. Ultrasensitive immunomagnetic reduction was applied to assay these proteins in the plasma. Results: The levels of plasma Aβ_1–40, Tau, and α-synuclein did not significantly change until 8 h after blood draw when stored at room temperature. Plasma Aβ_1–42 levels did not change significantly after 8 h of storage at room temperature before blood processing. Higher storage temperatures, such as 30°C, for blood samples accelerated the significant variations in the measured concentrations of Aβ_1–40, Tau, and α-synuclein in plasma. Conclusion: According to these results, for clinical practice, it is suggested that blood samples be stored at room temperature for no longer than 4.5 h after blood draw until centrifugation for the assay of dementia biomarkers in plasma.

Plasma Levels of α-Synuclein, Aβ-40 and T-tau as Biomarkers to Predict Cognitive Impairment in Parkinson's Disease.

ObjectiveIn this study, we assessed plasma biomarkers to identify cognitive impairment in Parkinson’s disease (PD) patients by applying ultra-sensitive immunomagnetic reduction-based immunoassay (IMR).MethodsThe study enrolled 60 PD patients and 28 age- and sex-matched normal controls. Complete cognitive function assessments were performed on participants using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating. PD patients with an MMSE score of ≦26 were defined as having cognitive impairment. Meanwhile, a 99mTc-TRODAT-1 scan was performed and plasma levels of Aβ-40, Aβ-42, T-tau, and α-synuclein were evaluated using IMR, subsequent correlation analyses were then performed.ResultsCompared with normal adults, PD patients have higher plasma levels of α-synuclein and T-tau, and a lower level of Aβ-40 (p < 0.05). Plasma levels of α-synuclein (r = −0.323, p = 0.002), Aβ-40 (r = 0.276, p = 0.01), and T-tau (r = −0.322, p = 0.002) are significantly correlated with MMSE scores. The TRODAT scan results, including visual inspection and quantification, revealed significant correlations between Aβ-40 and PD. Multiple regression analysis showed that the plasma levels of Aβ-40 (OR = 0.921, 95% CI = 0.879–0.962), α-synuclein (OR = 3.016, 95% CI = 1.703–5.339), and T-tau (OR = 1.069, 95% CI = 1.026–1.115) were independently associated with PD patients with cognitive impairment. The cutoff values for predicting cognitive deficits in PD patients were 45.101 pg/ml of Aβ-40, (Area under curve (AUC) = 0.791), 0.389 pg/ml of α-synuclein, (AUC = 0.790), and 30.555 pg/ml of T-tau (AUC = 0.726).ConclusionPlasma levels of α-synuclein, Aβ-40, and T-tau are potential biomarkers to detect cognitive impairment in PD patients.

Gesell Developmental Schedules scores and the relevant factors in children with Down syndrome.

Background Down syndrome (DS) is a common chromosomal disease resulting in neurodegeneration. Cognitive competence has been assessed among adults with DS using various methods because DS patients have a tendency to develop Alzheimer's disease (AD) after middle age. However, research describing cognitive assessments in DS children is not as many as in DS adults, let alone with regard to performed analyses to determine factors that predict cognitive assessments. In this study, we evaluated the Gesell Developmental Schedules (GDS) scores and their associations with the relevant biochemical indicators and demographic factors in DS children. Methods All the subjects underwent GDS testing. The plasma amyloid-β (Aβ) peptide and serum vitamin A (VA) values were measured with enzyme-linked immunosorbent assay and high-performance liquid chromatography, and in the meanwhile, the demographic information of the subjects was collected. Results Forty-six DS children were recruited for this study. The GDS scores of children with DS were lower than those in children without DS. The plasma Aβ40 and Aβ42 levels were negatively associated with the GDS scores. Moreover, the GDS scores of the non-VA deficiency (NVAD) group were significantly higher than those of the VA deficiency (VAD) group. Certain demographic characteristics, such as the paternal labor intensity and paternal educational status, were relevant factors with regard to the GDS scores of the DS children. Conclusions This study determined that DS children exhibited abnormal GDS scores which indicated developmental delay of children with DS; the levels of plasma Aβ40, Aβ42 and serum VA were influential biochemical indicators and the paternal labor intensity and educational status were related demographic factors.

The overnight reduction of amyloid β 1-42 plasma levels is diminished by the extent of sleep fragmentation, sAPP-β, and APOE ε4 in psychiatrists on call.

In mice there might be an association between sleep deprivation and amyloid β plasma levels. Hence, we examined whether amyloid plasma levels are associated with sleep duration or fragmentation in 17 psychiatrists on-call. Amyloid β (Aβ)42, Aβ40, and soluble amyloid precursor protein β (sAPP-β) plasma concentrations were measured at the beginning and end of 90 on-call nights, and analyzed using generalized linear models. In on-call nights, a 10.7% reduction of Aβ42 was revealed overnight. Every single short sleep interruption diminished this reduction by 5.4%, as well as every pg/mL of sAPP-β by 1.2%, each copy of APOE ε4 by 10.6%, and each year of professional experience by 3.0%. The extent of sleep fragmentation diminishes the physiological overnight reduction of Aβ42 but not Aβ40 plasma levels in the same direction as the enzyme for Aβ42 production, the genetic risk factor for Alzheimer's disease (AD), and on-call experience. Might on-call duty and sleep fragmentation in general alter the risk for AD?