International Journal of Geriatric Psychiatry, Год журнала: 2024, Номер 39(2)
Опубликована: Фев. 1, 2024
It is important to determine if cognitive measures identified as being prognostic in dementia research cohorts also have utility memory clinics. We aimed identify with the greatest power predict future Alzheimer's disease (AD) a clinical setting where expensive biomarkers are not widely available.
Язык: Английский
Alzheimer s & Dementia, Год журнала: 2022, Номер 19(4), С. 1403 - 1414
Опубликована: Сен. 24, 2022
Abstract Introduction Plasma biomarkers will likely revolutionize the diagnostic work‐up of Alzheimer's disease (AD) globally. Before widespread use, we need to determine if confounding factors affect levels these biomarkers, and their clinical utility. Methods Participants with plasma CSF creatinine, body mass index (BMI), medical history data were included (BioFINDER‐1: n = 748, BioFINDER‐2: 421). We measured beta‐amyloid (Aβ42, Aβ40), phosphorylated tau (p‐tau217, p‐tau181), neurofilament light (NfL), glial fibrillary acidic protein (GFAP). Results In both cohorts, creatinine BMI main associated NfL, GFAP, a lesser extent p‐tau. However, adjustment for had only minor effects in models predicting either corresponding or subsequent development dementia. Discussion Creatinine are related certain levels, but they do not have clinically relevant vast majority individuals. Highlights (BMI) biomarker levels. Adjusting has influence on plasma‐cerebrospinal fluid (CSF) associations. prediction dementia using biomarkers.
Язык: Английский
Процитировано
132
Alzheimer s Research & Therapy, Год журнала: 2023, Номер 15(1)
Опубликована: Фев. 8, 2023
Failures in drug trials strengthen the necessity to further determine neuropathological events during development of Alzheimer's disease (AD). We sought investigate dynamic changes and performance plasma biomarkers across entire continuum Chinese population.Plasma amyloid-β (Αβ)42, Aβ40, Aβ42/Aβ40, phosphorylated tau (p-tau)181, neurofilament light (NfL), glial fibrillary acidic protein (GFAP) were measured utilizing ultrasensitive single-molecule array technology AD (n=206), wherein Aβ status was defined by values cerebrospinal fluid (CSF) Aβ42 or positron emission tomography (PET). Their trajectories compared with those putative CSF biomarkers.Plasma GFAP p-tau181 increased only Aβ-positive individuals throughout aging, whereas NfL aging regardless status. Among studied, one that changed first. It had a prominent elevation early cognitively unimpaired (CU) A+T- phase (CU phase: 97.10±41.29 pg/ml; CU A-T- 49.18±14.39 p<0.001). From preclinical symptomatic stages AD, started rise sharply as soon became abnormal continued increase until reaching its highest level dementia phase. The greatest slope change seen GFAP. This is followed total-tau, and, lesser extent, then p-tau181. In contrast, NfL, Aβ42, Aβ40 less pronounced. Of note, these exhibited smaller ranges than their counterparts, except for which opposite. Plasma tightly associated pathologies amyloid tracer uptake widespread brain areas. could accurately identify (area under curve (AUC)=0.911) PET (AUC=0.971) positivity. also performed well discriminating (AUC=0.916), discriminative accuracy relatively low other biomarkers.This study first delineate population, providing important implications future targeting facilitate prevention treatment.
Язык: Английский
Процитировано
56
Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)
Опубликована: Май 15, 2024
Abstract Alzheimer’s disease (AD), the most common form of dementia, remains challenging to understand and treat despite decades research clinical investigation. This might be partly due a lack widely available cost-effective modalities for diagnosis prognosis. Recently, blood-based AD biomarker field has seen significant progress driven by technological advances, mainly improved analytical sensitivity precision assays measurement platforms. Several biomarkers have shown high potential accurately detecting pathophysiology. As result, there been considerable interest in applying these prognosis, as surrogate metrics investigate impact various covariates on pathophysiology accelerate therapeutic trials monitor treatment effects. However, standardization how blood samples collected, processed, stored analyzed reported can affect reproducibility measurements, potentially hindering toward their widespread use settings. To help address issues, we provide fundamental guidelines developed according recent findings sample handling measurements. These cover important considerations including study design, collection, processing, biobanking, measurement, result reporting. Furthermore, proposed include best practices appropriate procedures genetic ribonucleic acid analyses. While focus key AT(N) criteria (e.g., amyloid-beta [Aβ]40, Aβ42, Aβ42/40 ratio, total-tau, phosphorylated-tau, neurofilament light chain, brain-derived tau glial fibrillary acidic protein), anticipate that will generally applicable other types biomarkers. We also assist investigators planning executing research, enabling harmonization improve comparability across studies.
Язык: Английский
Процитировано
18
Molecular Neurodegeneration, Год журнала: 2021, Номер 16(1)
Опубликована: Ноя. 6, 2021
Abstract Multi-pathway approaches for the treatment of complex polygenic disorders are emerging as alternatives to classical monotarget therapies and microRNAs particular interest in that regard. MicroRNA research has come a long way from their initial discovery cumulative appreciation regulatory potential healthy diseased brain. However, systematic interrogation putative therapeutic or toxic effects (models of) Alzheimer’s disease is currently missing fundamental findings yet be translated into clinical applications. Here, we review literature summarize knowledge on microRNA regulation pathophysiology critically discuss whether what extent these increasing insights can exploited development microRNA-based therapeutics clinic.
Язык: Английский
Процитировано
92
Journal of Internal Medicine, Год журнала: 2021, Номер 290(3), С. 583 - 601
Опубликована: Май 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.
Язык: Английский
Процитировано
78
Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Год журнала: 2022, Номер 14(1)
Опубликована: Янв. 1, 2022
Abstract Biomarker testing is recommended for the accurate and timely diagnosis of Alzheimer's disease (AD). Using illustrative case narratives we consider how cerebrospinal fluid (CSF) biomarker tests may be used in different presentations cognitive impairment to facilitate differential diagnosis, improving diagnostic accuracy, providing prognostic information, guiding personalized management diverse scenarios. Evidence shows that (1) CSF ratios are superior amyloid beta (Aβ)1‐42 alone; (2) concordance positron emission tomography (PET) better than Aβ1‐42 (3) phosphorylated tau (p‐tau)/Aβ1‐42 ratio p‐tau alone. biomarkers exclusion AD as underlying cause impairment, at an early stage, individuals presenting with other neuropsychiatric symptoms, atypical presentation, clinical trial enrichment. Highlights Cerebrospinal (AD) underused outside specialist centers. improve AD. (amyloid [Aβ]1‐42/Aβ1‐40 tau/Aβ1‐42) perform single markers. produce fewer false‐negative false‐positive results individual should included work‐up mild due
Язык: Английский
Процитировано
68
Biosensors and Bioelectronics, Год журнала: 2022, Номер 210, С. 114278 - 114278
Опубликована: Апрель 13, 2022
Язык: Английский
Процитировано
53
Neuron, Год журнала: 2022, Номер 110(6), С. 1009 - 1022.e4
Опубликована: Янв. 6, 2022
Язык: Английский
Процитировано
52
Alzheimer s Research & Therapy, Год журнала: 2022, Номер 14(1)
Опубликована: Май 11, 2022
Abstract Background Blood phosphorylated tau (p-tau) forms are promising Alzheimer’s disease (AD) biomarkers, but validation in matrices other than ethylenediaminetetraacetic acid (EDTA) plasma is limited. Firstly, we assessed the diagnostic potential of p-tau231 and p-tau181 paired serum samples. Secondly, compared cerebrospinal fluid (CSF) samples from biomarker-positive AD biomarker-negative control participants. Methods We studied three independent cohorts ( n =115 total): 1 2 included individuals with serum, while cohort 3 CSF. Blood-based were measured using in-house or commercial single molecule array (Simoa) methods. Results Serum two- to three-fold increased versus controls P ≤0.0008). separated groups area under curve (AUC) 82.2% (cohort 3) 88.2% 1) 90.2% for plasma. Similarly, showed AUC 89.6% 89.8% 85.4% 1). P-tau231 correlated slightly better (rho=0.92 1, 0.93 (rho=0.88, Within-individual (Quanterix) concentrations twice higher (in-house, Gothenburg) levels not statistically different. Bland-Altman plots revealed that relative difference between serum/plasma was larger lower range. P-tau strongly each (rho=0.75–0.93) as well CSF Aβ 42 (rho= −0.56 −0.59), p-tau total-tau (rho=0.53–0.73). Based on results, it seems possible reflects same pool brain-secreted CSF; estimated less 2% found being both AD. Conclusions Comparable performances strong correlations pairs suggest analyses can be expanded research hospital systems prefer blood matrices. However, absolute biomarker may interchangeable, indicating should used independently. These results validated cohorts.
Язык: Английский
Процитировано
50
Biomedicines, Год журнала: 2022, Номер 10(4), С. 850 - 850
Опубликована: Апрель 5, 2022
In the 115 years since discovery of Alzheimer’s disease (AD), our knowledge, diagnosis, and therapeutics have significantly improved. Biomarkers are primary tools for clinical research, diagnostics, therapeutic monitoring in trials. They provide much insightful information, while they not clinically used routinely, help us to understand mechanisms this disease. This review charts journey AD biomarker development from cerebrospinal fluid (CSF) amyloid-beta 1-42 (Aβ42), total tau (T-tau), phosphorylated (p-tau) biomarkers imaging technologies next generation biomarkers. We also discuss advanced high-sensitivity assay platforms CSF Aβ42, T-tau, p-tau, blood analysis. The recently proposed Aβ deposition/tau biomarker/neurodegeneration or neuronal injury (ATN) scheme might facilitate definition biological status underpinning offer a common language among researchers across biochemical imaging. Moreover, we highlight blood-based that scalable alternative through cost-saving reduced invasiveness, may an understanding initiation development. different groups candidates, their advantages limitations, paths forward, identification analysis validation. valid implementation future diagnostics.
Язык: Английский
Процитировано
40