OBJECTIVES: The core cerebrospinal fluid (CSF) biomarkers; total tau (tTau), phospho-tau (pTau), amyloid β 1-42 (Aβ 1-42), and the Aβ 1-42/Aβ 1-40 ratio have transformed Alzheimer's disease (AD) research and are today increasingly used in clinical routine laboratories as diagnostic tools. Fully automated immunoassay instruments with ready-to-use assay kits and calibrators has simplified their analysis and improved reproducibility of measurements. We evaluated the analytical performance of the fully automated immunoassay instrument LUMIPULSE G (Fujirebio) for measurement of the four core AD CSF biomarkers and determined cutpoints for AD diagnosis. METHODS: Comparison of the LUMIPULSE G assays was performed with the established INNOTEST ELISAs (Fujirebio) for hTau Ag, pTau 181, β-amyloid 1-42, and with V-PLEX Plus Aβ Peptide Panel 1 (6E10) (Meso Scale Discovery) for Aβ 1-42/Aβ 1-40, as well as with a LC-MS reference method for Aβ 1-42. Intra- and inter-laboratory reproducibility was evaluated for all assays. Clinical cutpoints for Aβ 1-42, tTau, and pTau was determined by analysis of three cohorts of clinically diagnosed patients, comprising 651 CSF samples. For the Aβ 1-42/Aβ 1-40 ratio, the cutpoint was determined by mixture model analysis of 2,782 CSF samples. RESULTS: The LUMIPULSE G assays showed strong correlation to all other immunoassays (r>0.93 for all assays). The repeatability (intra-laboratory) CVs ranged between 2.0 and 5.6%, with the highest variation observed for β-amyloid 1-40. The reproducibility (inter-laboratory) CVs ranged between 2.1 and 6.5%, with the highest variation observed for β-amyloid 1-42. The clinical cutpoints for AD were determined to be 409 ng/L for total tau, 50.2 ng/L for pTau 181, 526 ng/L for β-amyloid 1-42, and 0.072 for the Aβ 1-42/Aβ 1-40 ratio. CONCLUSIONS: Our results suggest that the LUMIPULSE G assays for the CSF AD biomarkers are fit for purpose in clinical laboratory practice. Further, they corroborate earlier presented reference limits for the biomarkers.
- MeSH
- Alzheimerova nemoc * mozkomíšní mok diagnóza MeSH
- amyloidní beta-protein mozkomíšní mok MeSH
- biologické markery mozkomíšní mok MeSH
- imunoanalýza metody MeSH
- lidé MeSH
- peptidové fragmenty mozkomíšní mok MeSH
- proteiny tau mozkomíšní mok MeSH
- reprodukovatelnost výsledků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
To identify knowledge gaps regarding new-onset agitation and impulsivity prior to onset of cognitive impairment or dementia the International Society to Advance Alzheimer's Research and Treatment Neuropsychiatric Syndromes (NPS) Professional Interest Area conducted a scoping review. Extending a series of reviews exploring the pre-dementia risk syndrome Mild Behavioral Impairment (MBI), we focused on late-onset agitation and impulsivity (the MBI impulse dyscontrol domain) and risk of incident cognitive decline and dementia. This scoping review of agitation and impulsivity pre-dementia syndromes summarizes the current biomedical literature in terms of epidemiology, diagnosis and measurement, neurobiology, neuroimaging, biomarkers, course and prognosis, treatment, and ongoing clinical trials. Validations for pre-dementia scales such as the MBI Checklist, and incorporation into longitudinal and intervention trials, are needed to better understand impulse dyscontrol as a risk factor for mild cognitive impairment and dementia.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
2nd ed. iv, 164 p. : il. ; 21 cm
- MeSH
- Alzheimerova nemoc diagnóza terapie MeSH
- demence diagnóza terapie MeSH
- dlouhodobá péče MeSH
- management nemoci MeSH
- neurokognitivní poruchy MeSH
- Parkinsonova nemoc diagnóza terapie MeSH
- rizikové faktory MeSH
- Publikační typ
- monografie MeSH
- Konspekt
- Psychiatrie
- NLK Obory
- neurologie
- psychiatrie
vii, 168 s. : il., tab. ; 20 cm
2nd ed. XII, 386 s. : il. ; 28 cm
xviii, 166 stran : ilustrace, tabulky ; 22 cm
- MeSH
- Alzheimerova nemoc farmakoterapie MeSH
- léčivé přípravky MeSH
- Publikační typ
- sborníky MeSH
- Konspekt
- Farmacie. Farmakologie
- NLK Obory
- farmakoterapie
- neurologie
- NLK Publikační typ
- kolektivní monografie
XI, 372 s. : tab., grafy, fot. ; 26 cm
