Search

High-throughput proteomic platforms are crucial to identify novel Alzheimer's disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan ® 7k) and antibody-based (Olink ® Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona real-world cohort. Intra- and inter-platform reproducibility were evaluated through correlations between two independent SomaScan ® assays analyzing the same samples, and between SomaScan ® and Olink ® results. Association analyses were performed between proteomic measures, CSF biological traits, sample demographics, and AD endophenotypes. Our 12-category metric of reproducibility combining correlation analyses identified 2428 highly reproducible SomaScan CSF measures, with over 600 proteins well reproduced on another proteomic platform. The association analyses among AD clinical phenotypes revealed that the significant associations mainly involved reproducible proteins. The validation of reproducibility in these novel proteomics platforms, measured using this scarce biomaterial, is essential for accurate analysis and proper interpretation of innovative results. This classification metric could enhance confidence in multiplexed proteomic platforms and improve the design of future panels.

Introduction: Understanding the impact of biomarker-based dementia risk estimation in people with mild cognitive impairment (MCI) and their care partners is critical for patient care., Methods: MCI patients and study partners were counseled on Alzheimer's disease (AD) biomarker and dementia risk was disclosed. Data on mood, quality of life (QoL), and satisfaction with life (SwL) were obtained 1 week and 3 months after disclosure., Results: Seventy-five dyads were enrolled, and two-thirds of the patients opted for biomarker testing. None of the participants experienced clinically relevant depression or anxiety after disclosure. All dyads reported moderate to high QoL and SwL throughout the study. Patients reported more subthreshold depressive symptoms 1 week and lower QoL and SwL 3 months after disclosure. In patients, depression (odds ratio [OR]: 0.76) and anxiety (OR: 0.81) were significant predictors for the decision against biomarker testing., Discussion: No major psychological harm is to be expected in MCI patients and care partners after dementia risk disclosure., Trial Registration: This study is registered in the German clinical trials register (Deutsches Register Klinischer Studien, DRKS): http://www.drks.de/DRKS00011155, DRKS registration number: DRKS00011155, date of registration: 18.08.2017., Highlights: Patients with mild cognitive impairment (MCI) and study partners were counseled on Alzheimer's disease (AD) biomarker-based dementia risk estimation. About two-thirds of patients opted for biomarker testing and received their dementia risk based on their AD biomarker status. Patients who decided in favor or against CSF biomarker testing differed in psychological features. We did not observe major psychological harm after the dementia risk disclosure. Coping strategies were associated with better subsequent mood and well-being in all participants., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

High-throughput proteomic platforms are crucial to identify novel Alzheimer's disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan® 7k) and antibody-based (Olink® Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona real-world cohort. Intra- and inter-platform reproducibility were evaluated through correlations between two independent SomaScan® assays analyzing the same samples, and between SomaScan® and Olink® results. Association analyses were performed between proteomic measures, CSF biological traits, sample demographics, and AD endophenotypes. Our 12-category metric of reproducibility combining correlation analyses identified 2428 highly reproducible SomaScan CSF measures, with over 600 proteins well reproduced on another proteomic platform. The association analyses among AD clinical phenotypes revealed that the significant associations mainly involved reproducible proteins. The validation of reproducibility in these novel proteomics platforms, measured using this scarce biomaterial, is essential for accurate analysis and proper interpretation of innovative results. This classification metric could enhance confidence in multiplexed proteomic platforms and improve the design of future panels. [ABSTRACT FROM AUTHOR]

Building on previous studies that report thinning of the macula in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients, the use of optical coherence tomography (OCT) has been proposed as a potential biomarker for AD. However, other studies contradict these results. A total of 930 participants (414 cognitively healthy people, 192 with probable amnestic MCI, and 324 probable AD patients) from a memory clinic were consecutively included in this study and underwent a spectral domain OCT scan (Maestro, Topcon) to assess total macular volume and thickness. Macular width measurements were also taken in several subregions (central, inner, and outer rings) and in layers such as the retinal nerve fiber (RNFL) and ganglion cell (CGL). The study employed a design of high ecological validity, with adjustment by age, education, sex, and OCT image quality. AD, MCI, and control groups did not significantly vary with regard to volume and retinal thickness in different layers. When these groups were compared, multivariate-adjusted analysis disclosed no significant differences in total (p = 0.564), CGL (p = 0.267), RNFL (p = 0.574), and macular thickness and volume (p = 0.380). The only macular regions showing significant differences were the superior (p = 0.040) and nasal (p = 0.040) sectors of the inner macular ring. However, adjustment for multiple comparisons nullified this significance. These results are not supporting existing claims for the usefulness of macular thickness as a biomarker of cognitive impairment in a memory unit. OCT biomarkers for AD should be subject to further longitudinal testing. [ABSTRACT FROM AUTHOR]

Transmembrane Protein 106B SNP rs1990622 was recently shown to modify the risk of frontotemporal lobar degeneration with TDP-43 inclusions (FTD-TDP). An independent replication study of this genetic variant was performed in 381 individuals from Catalonia (Spain). By applying a recessive model, a tendency toward an association with FTD risk was observed in our case-control study (age- and gender-adjusted odds ratio = 0.57; p = 0.082). Importantly, meta-analysis of available studies also supports a recessive effect for rs1990622 CC genotype (OR = 0.70; CI 95% [0.57-0.85]; p = 0.0003) and demonstrates the existence of statistical heterogeneity due to an inherent pathological heterogeneity between series (p = 0.00014). We conclude that TMEM106B is associated with FTD, although the extent of this effect is difficult to be estimated by using clinical FTD series. [ABSTRACT FROM AUTHOR]