Year: 2014
Type: article
Abstract: Two amyloid biomarkers are by hand, amyloid PET and CSF Aβ42. This presentation will provide update on current knowledge on these biomarkers and communicate new data on their performance as tools for diagnosis, to monitor Aβ metabolism and aggregation in clinical trials, and to study AD pathogenesis in man. CSF Aβ42 by ELISA and SRM mass-spectrometry method for absolute quantification.Plasma Aβ42 measurement by ultra-sensitive single-molecule digital ELISA (SiMoA).Clinical and population-based cohorts of cognitively normal elderly and patients with mild cognitive impairment (MCI) and AD with longitudinal follow-up. Clinical cohort of patients resuscitated from cardiac arrest. Amyloid PET and CSF Aβ42 show very high concordance (>90%) to identify presence or absence of cortical amyloid deposition, and thus identical diagnostic performance.G lobal cortical and regional (e.g. frontal, posterior cingulate) cortical amyloid PET evaluations show the same results.CSF Aβ42 shows an APOE e 4 gene-dose dependent decrease, both in AD patients and controls, which is only found in individuals >50 years, and disappear when stratifying for amyloid PET negativity or positivity.CSF Aβ42 starts to decline in cognitive normal APOE e 4 homozygotes before age 60.SRM mass spectrometric analysis of Aβ42 show excellent analytical precision with high correlations between labs. The SiMoA technique is highly sensitive, and show excellent performance down to concentrations that are >200 times lower than ELISA methods. Amyloid PET and CSF Aβ42 can be used interchangeably; regional evaluations give no additional information than g lobal cortical measures.- Cortical Aβ deposition in e 4 carriers explain both lower CSF Aβ42 in APOE e 4 carriers and the age-related drop in e 4 homozygotes.- SRM mass-spectrometric analysis gives an absolute quantification without matrix effects, and is suitable as a reference measurement procedure (RMP) for Aβ42. This technique will, together with the CSF-based reference material, be essential for standardization of immunoassays. Aβ42 assays on fully automated lab-analyzers will provide the basis for general cut-off levels and short (<1h.) turn-around times. Plasma Aβ42 shows a marked increase after cardiac arrest but no change during treatment with imatinib.
Source: Alzheimer s & Dementia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1987758133