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1.
Alzheimers Dement ; 20(8): 5132-5142, 2024 08.
Article in English | MEDLINE | ID: mdl-38940303

ABSTRACT

INTRODUCTION: Blood-based biomarkers are a cost-effective and minimally invasive method for diagnosing the early and preclinical stages of amyloid positivity (AP). Our study aims to investigate our novel immunoprecipitation-immunoassay (IP-IA) as a test for predicting cognitive decline. METHODS: We measured levels of amyloid beta (Aß)X-40 and AßX-42 in immunoprecipitated eluates from the DELCODE cohort. Receiver-operating characteristic (ROC) curves, regression analyses, and Cox proportional hazard regression models were constructed to predict AP by Aß42/40 classification in cerebrospinal fluid (CSF) and conversion to mild cognitive impairment (MCI) or dementia. RESULTS: We detected a significant correlation between AßX-42/X-40 in plasma and CSF (r = 0.473). Mixed-modeling analysis revealed a substantial prediction of AßX-42/X-40 with an area under the curve (AUC) of 0.81 for AP (sensitivity: 0.79, specificity: 0.74, positive predictive value [PPV]: 0.71, negative predictive value [NPV]: 0.81). In addition, lower AßX-42/X-40 ratios were associated with negative PACC5 slopes, suggesting cognitive decline. DISCUSSION: Our results suggest that assessing the plasma AßX-42/X-40 ratio via our semiautomated IP-IA is a promising biomarker when examining patients with early or preclinical AD. HIGHLIGHTS: New plasma Aß42/Aß40 measurement using immunoprecipitation-immunoassay Plasma Aß42/Aß40 associated with longitudinal cognitive decline Promising biomarker to detect subjective cognitive decline at-risk for brain amyloid positivity.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Biomarkers , Cognitive Dysfunction , Peptide Fragments , Humans , Amyloid beta-Peptides/blood , Amyloid beta-Peptides/cerebrospinal fluid , Alzheimer Disease/blood , Alzheimer Disease/diagnosis , Alzheimer Disease/cerebrospinal fluid , Cognitive Dysfunction/blood , Cognitive Dysfunction/cerebrospinal fluid , Cognitive Dysfunction/diagnosis , Male , Female , Aged , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Peptide Fragments/blood , Peptide Fragments/cerebrospinal fluid , Middle Aged , ROC Curve , Immunoprecipitation , Disease Progression
2.
Eur Arch Psychiatry Clin Neurosci ; 263(8): 695-701, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23545941

ABSTRACT

The German Association for Psychiatry and Psychotherapy (DGPPN) has committed itself to establish a prospective national cohort of patients with major psychiatric disorders, the so-called DGPPN-Cohort. This project will enable the scientific exploitation of high-quality data and biomaterial from psychiatric patients for research. It will be set up using harmonised data sets and procedures for sample generation and guided by transparent rules for data access and data sharing regarding the central research database. While the main focus lies on biological research, it will be open to all kinds of scientific investigations, including epidemiological, clinical or health-service research.


Subject(s)
Cooperative Behavior , Mental Disorders , Psychiatry , Psychotherapy/methods , Psychotherapy/standards , Cohort Studies , Female , Germany , Humans , Male , Mental Disorders/diagnosis , Mental Disorders/psychology , Mental Disorders/therapy , Societies, Medical
3.
Brain Commun ; 5(5): fcad263, 2023.
Article in English | MEDLINE | ID: mdl-37901043

ABSTRACT

Blood-based analysis of amyloid-ß is increasingly applied to incrementally establish diagnostic tests for Alzheimer's disease. To this aim, it is necessary to determine factors that can alter blood-based concentrations of amyloid-ß. We cross-sectionally analysed amyloid-ß-40 and amyloid-ß-42 concentrations and the 40/42 ratio in 440 community-dwelling adults and associations with body mass index, waist-to-height ratio and body composition assessed using bioelectrical impedance analysis. Body mass index and waist-to-height ratio were inversely associated with plasma amyloid-ß-42 concentrations. Body fat mass, but not body cell mass and extracellular mass, was inversely associated with amyloid-ß-42 levels. The results indicate that plasma concentrations of amyloid-ß-42 are lower in those with increased body mass index and body fat, and associations with amyloid-ß-40 did not reach significance after controlling for multiple testing. The findings support the use of body mass index as an easy-to-measure factor that should be accounted for in diagnostic models for plasma amyloid-ß.

4.
Alzheimers Res Ther ; 14(1): 127, 2022 09 07.
Article in English | MEDLINE | ID: mdl-36071505

ABSTRACT

BACKGROUND: Measurements of the amyloid-ß (Aß) 42/40 ratio in blood plasma may support the early diagnosis of Alzheimer's disease and aid in the selection of suitable participants in clinical trials. Here, we compared the diagnostic performance of fully automated prototype plasma Aß42/40 assays with and without pre-analytical sample workup by immunoprecipitation. METHODS: A pre-selected clinical sample comprising 42 subjects with normal and 38 subjects with low cerebrospinal fluid (CSF) Aß42/40 ratios was studied. The plasma Aß42/40 ratios were determined with fully automated prototype Elecsys® immunoassays (Roche Diagnostics GmbH, Penzberg, Germany) by direct measurements in EDTA plasma or after pre-analytical Aß immunoprecipitation. The diagnostic performance for the detection of abnormal CSF Aß42/40 was analyzed by receiver operating characteristic (ROC) analysis. In an additional post hoc analysis, a biomarker-supported clinical diagnosis was used as a second endpoint. RESULTS: Pre-analytical immunoprecipitation resulted in a significant increase in the area under the ROC curve (AUC) from 0.73 to 0.88 (p = 0.01547) for identifying subjects with abnormal CSF Aß42/40. A similar improvement in the diagnostic performance by pre-analytical immunoprecipitation was also observed when a biomarker-supported clinical diagnosis was used as a second endpoint (AUC increase from 0.77 to 0.92, p = 0.01576). CONCLUSIONS: Our preliminary observations indicate that pre-analytical Aß immunoprecipitation can improve the diagnostic performance of plasma Aß assays for detecting brain amyloid pathology. The findings may aid in the further development of blood-based immunoassays for Alzheimer's disease ultimately suitable for screening and routine use.


Subject(s)
Alzheimer Disease , Alzheimer Disease/pathology , Amyloid beta-Peptides/cerebrospinal fluid , Biomarkers/cerebrospinal fluid , Humans , Immunoprecipitation , Peptide Fragments/cerebrospinal fluid , Plasma
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