The performance of plasma amyloid beta measurements in identifying amyloid plaques in Alzheimer’s disease: a literature review

Alzheimer s Research & Therapy, Journal Year: 2022, Volume and Issue: 14(1)

Published: Dec. 27, 2022

Abstract The extracellular buildup of amyloid beta (Aβ) plaques in the brain is a hallmark Alzheimer’s disease (AD). Detection Aβ pathology essential for AD diagnosis and identifying recruiting research participants clinical trials evaluating disease-modifying therapies. Currently, diagnoses are usually made by assessments, although detection with positron emission tomography (PET) scans or cerebrospinal fluid (CSF) analysis can be used specialty clinics. These measures aggregation, e.g. plaques, protofibrils, oligomers, medically invasive often only available at specialized medical centers not covered insurance, PET costly. Therefore, major goal recent years has been to identify blood-based biomarkers that accurately detect cost-effective, minimally procedures. To assess performance plasma assays predicting burden central nervous system (CNS), this review compares twenty-one different manuscripts measurements 42 40 amino acid-long (Aβ42 Aβ40) predict CNS status. Methodologies quantitate Aβ42 peptides blood via immunoassay immunoprecipitation-mass spectrometry (IP-MS) were considered, their ability distinguish amyloidosis compared CSF as reference standards was evaluated. Recent studies indicate some IP-MS perform well precisely measuring detecting aggregates.

Language: Английский

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Predicting amyloid PET and tau PET stages with plasma biomarkers

Brain, Journal Year: 2023, Volume and Issue: 146(5), P. 2029 - 2044

Published: Feb. 15, 2023

Abstract Staging the severity of Alzheimer’s disease pathology using biomarkers is useful for therapeutic trials and clinical prognosis. Disease staging with amyloid tau PET has face validity; however, this would be more practical plasma biomarkers. Our objectives were, first, to examine approaches and, second, prediction stages Participants (n = 1136) were enrolled in either Mayo Clinic Study Aging or Research Center; had a concurrent PET, blood draw; met criteria cognitively unimpaired 864), mild cognitive impairment 148) syndrome dementia 124). The latter two groups combined into impaired group 272). We used multinomial regression models estimate discrimination [concordance (C) statistics] among three (low, intermediate, high), four (Braak 0, 1–2, 3–4, 5–6) stage (none/low versus intermediate/high severity) as predictors separately within individuals. Plasma analytes, p-tau181, Aβ1–42 Aβ1–40 (analysed Aβ42/Aβ40 ratio), glial fibrillary acidic protein neurofilament light chain measured on HD-X Simoa Quanterix platform. p-tau217 was also subset 355) participants Lilly Meso Scale Discovery assay. Models all analytes along risk factors (age, sex APOE) most often provided best (C 0.78–0.82). p-tau181 similar 0.72–0.85 C 0.73–0.86). Discriminating proxy from none/low neuropathological change excellent but not better than only 0.88 0.87 0.91 0.90 impaired). outperformed assay discriminating high intermediate 0.85 0.74) did improve over model 0.83). can discriminate between surrogate accuracy acceptable range. Combinations are single many predictions exception that alone usually performed equivalently combinations discrimination.

Language: Английский

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Sex and gender differences in cognitive resilience to aging and Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(8), P. 5695 - 5719

Published: July 5, 2024

Abstract Sex and gender—biological social constructs—significantly impact the prevalence of protective risk factors, influencing burden Alzheimer's disease (AD; amyloid beta tau) other pathologies (e.g., cerebrovascular disease) which ultimately shape cognitive trajectories. Understanding interplay these factors is central to understanding resilience resistance mechanisms explaining maintained function reduced pathology accumulation in aging AD. In this narrative review, ADDRESS! Special Interest Group (Alzheimer's Association) adopted a multidisciplinary approach provide foundations recommendations for future research into sex‐ gender‐specific drivers resilience, including sex/gender‐oriented review genetics, AD non‐AD pathologies, brain structure function, animal research. We urge field adopt sex/gender‐aware advance our intricate biological determinants consider sex/gender‐specific throughout stages. Highlights differences decline vary by age status. Initial evidence supports sex‐specific distinctions pathology. Findings suggest sex on cognition. There change transition clinical Gender warrant study: modifiable, immune, inflammatory, vascular.

Language: Английский

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An Update on Blood-Based Markers of Alzheimer’s Disease Using the SiMoA Platform

Neurology and Therapy, Journal Year: 2019, Volume and Issue: 8(S2), P. 73 - 82

Published: Dec. 1, 2019

The development of blood-based biomarkers Alzheimer's disease (AD) pathology as tools for screening the general population, and first step in a multistep process to determine which non-demented individuals are at greatest risk developing AD dementia, is essential. Proteins that reflective pathology, such amyloid beta 42 (Aβ42), tau proteins [total (T-tau) phosphorylated (P-tau)], neurofilament light chain (NfL), detectable blood. However, major challenge measuring these their concentrations much lower plasma or serum than cerebrospinal fluid. Single molecule array (SiMoA) an ultrasensitive technology can detect blood sub-femtomolar (i.e., 10−16 M). In this review, we focus on utility SiMoA assays measurement Aβ42, P-tau, T-tau, NfL levels discuss future directions.

Language: Английский

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OUP accepted manuscript

Brain, Journal Year: 2020, Volume and Issue: unknown

Published: Jan. 1, 2020

Alzheimer's disease has a preclinical stage when cerebral amyloid-b deposition occurs before symptoms emerge, and amyloid-b-targeted therapies may have maximum benefits.Existing status measurement techniques, including amyloid PET CSF testing, are difficult to deploy at scale, so blood biomarkers increasingly considered for screening.We compared three different blood-based techniques-liquid chromatography-mass spectrometry measures of plasma amyloid-b, single molecule array (Simoa) phospho-tau181-to detect cortical 18 F-florbetapir positivity (defined as standardized uptake value ratio 40.61 between predefined region interest eroded subcortical white matter) in dementia-free members Insight 46, substudy the population-based British 1946 birth cohort.We used logistic regression models with predictors status, or without age, sex APOE e4 carrier covariates.We generated receiver operating characteristics curves quantified areas under compare concordance tests PET.We determined test cut-off points using Youden's index, then estimated numbers needed screen obtain 100 PET-positive individuals.Of 502 individuals assessed, 441 complete data were included; 82 (18.6%) PET-positive.The area curve base model comprising was 0.695 (95% confidence interval: 0.628-0.762).The two best-performing Simoa 42/40 (0.620; 0.548-0.691)and phospho-tau181 (0.707; 0.646-0.768),but neither outperformed model.Mass performed significantly better than any other measure (amyloid-b 1-42/1-40 : 0.817; 0.770-0.864and composite: 0.820; 0.775-0.866).At point 0.095, mass detected 86.6% sensitivity 71.9% specificity.Without screening, from population similar prevalence 543 scans would need be performed.Screening require 940 individuals, whom 266 proceed scan.Using alone reduce these 623 243 respectively.Across theoretical range 10-50%, consistently proceeding scans, greater cost savings demonstrated lower prevalence.

Language: Английский

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Predictive Value of Routine Peripheral Blood Biomarkers in Alzheimer’s Disease

Frontiers in Aging Neuroscience, Journal Year: 2019, Volume and Issue: 11

Published: Dec. 4, 2019

Biomarker screening is of major significance for the early diagnosis and prevention Alzheimer's disease (AD). Routine peripheral blood parameters are easy to collect detect, making them ideal potential biomarkers. Thus, we aimed evaluate from routine as biomarkers AD.We enrolled 56 AD patients, 57 mild cognitive impairment (MCI) 59 healthy elderly controls. Receiver operating characteristic (ROC) curves were used assess diagnostic values in patients with impairment.There significant differences eight between groups. Logistic regression revealed that neutrophil% (odds ratio (OR) 1.34, 95% confidence interval [CI] 1.03-1.75, p = 0.031) neutrophil-to-lymphocyte (NLR; OR 6.27, CI 3.98-9.82, 0.003) differentiated controls (areas under curve [AUCs], 0.728 0.721) NLR (OR 1.93, 1.07-3.47, 0.028) mean platelet volume 1.67, 1.04-2.70, 0.036) MCI (AUCs, 0.60 0.638). There no effective distinguish MCI.Some may correlate impairment. Analysis these biomarkers, such NLR, be useful identification

Language: Английский

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Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis

Alzheimer s Research & Therapy, Journal Year: 2020, Volume and Issue: 12(1)

Published: Dec. 1, 2020

Blood-based amyloid biomarkers may provide a non-invasive, cost-effective and scalable manner for detecting cerebral amyloidosis in early disease stages.

Language: Английский

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Transitioning from cerebrospinal fluid to blood tests to facilitate diagnosis and disease monitoring in Alzheimer's disease

Journal of Internal Medicine, Journal Year: 2021, Volume and Issue: 290(3), P. 583 - 601

Published: May 22, 2021

Alzheimer's disease (AD) is increasingly prevalent worldwide, and disease-modifying treatments may soon be at hand; hence, now, more than ever, there a need to develop techniques that allow earlier secure diagnosis. Current biomarker-based guidelines for AD diagnosis, which have replaced the historical symptom-based guidelines, rely heavily on neuroimaging cerebrospinal fluid (CSF) sampling. While these greatly improved diagnostic accuracy of pathophysiology, they are less practical application in primary care, population-based epidemiological settings, or where resources limited. In contrast, blood accessible cost-effective source biomarkers AD. this review paper, using recently proposed amyloid, tau neurodegeneration [AT(N)] criteria as framework towards biological definition AD, we discuss recent advances biofluid-based biomarkers, with particular emphasis those potential translated into blood-based biomarkers. We provide an overview research conducted both CSF draw conclusions show promise. Given evidence collated review, plasma neurofilament light chain (N) phosphorylated (p-tau; T) translation clinical practice. However, p-tau requires comparisons between its various epitopes before can made one most robustly differentiates from non-AD dementias. Plasma amyloid beta (A) would prove invaluable early screening modality, but it very precise tests robust pre-analytical protocols.

Language: Английский

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Assessment of Plasma Amyloid-β_42/40and Cognitive Decline Among Community-Dwelling Older Adults

JAMA Network Open, Journal Year: 2020, Volume and Issue: 3(12), P. e2028634 - e2028634

Published: Dec. 17, 2020

Importance

Plasma measurement of amyloid-β (Aβ) peptides has been associated with cognitive function, but evidence its ability to identify decline is still scarce.

Objective

To investigate the associations between plasma Aβ_42/40and over time among community-dwelling older adults subjective memory concerns.

Design, Setting, and Participants

This multicenter cohort study used data from volunteers in 5-year Multidomain Alzheimer Preventive Trial (MAPT). Participants were aged 70 years or observed for a median (interquartile range) 3.9 (2.0-4.0) years. Recruitment participants started May 2008 ended February 2011. Follow-up April 2016. Data analysis was conducted October 2020.

Exposure

Aβ₄₂and Aβ₄₀were measured at 12 months 448 (92.8%) 24 rest. The moment Aβ assessment defined as baseline this study.

Main Outcomes Measures

Cognitive function assessed 12, 24, 36, 48, 60 by composite score based on 4 tests; Mini Mental State Examination (MMSE); Clinical Dementia Rating, sum boxes; Disease Cooperative Study–Activities Daily Living. Mixed-effect linear regressions performed.

Results

A total 483 (median [IQR] age, 76.0 [73.0-80.0]; 286 [59.2%] women) analyzed. Of them, 161 (33.3%) classified low Aβ_42/40(≤0.107). After adjusting sex, education, body mass index, Geriatric Depression Scale score, apolipoprotein E ε4 genotype, MAPT intervention groups, Aβ_42/40was more pronounced (adjusted between-group mean difference: −0.20, 95% CI, −0.34 −0.07;P = .004) MMSE −0.59; −1.07 −0.11;P .02) during follow-up period compared group an Aβ_42/40ratio greater than 0.107.

Conclusions Relevance

In study, (measured multiple outcomes) time. Findings suggest that Aβ_42/40may be people risk decline, being alternative complex expensive measures, such positron emission tomography imaging cerebrospinal fluid measurement.

Language: Английский

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Neurovascular dysfunction and vascular amyloid accumulation as early events in Alzheimer's disease

Metabolic Brain Disease, Journal Year: 2021, Volume and Issue: 37(1), P. 39 - 50

Published: Aug. 18, 2021

Language: Английский

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