Profiling of plasma biomarkers in the context of memory assessment in a tertiary memory clinic.

Autor: Bucci M; Department of Neurobiology, Care Sciences and Society, Centre for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, SE-14183, Stockholm, Sweden.; Theme Inflammation and Aging, Karolinska University Hospital, SE-14186, Stockholm, Sweden., Bluma M; Department of Neurobiology, Care Sciences and Society, Centre for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, SE-14183, Stockholm, Sweden., Savitcheva I; Medical Radiation Physics and Nuclear Medicine, Karolinska University, SE-14186, Stockholm, Sweden., Ashton NJ; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-43180, Mölndal, Sweden., Chiotis K; Department of Neurobiology, Care Sciences and Society, Centre for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, SE-14183, Stockholm, Sweden.; Department of Neurology, Karolinska University Hospital, SE-14186, Stockholm, Sweden., Matton A; Department of Neurobiology, Care Sciences and Society, Centre for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, SE-14183, Stockholm, Sweden., Kivipelto M; Department of Neurobiology, Care Sciences and Society, Centre for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, SE-14183, Stockholm, Sweden.; Theme Inflammation and Aging, Karolinska University Hospital, SE-14186, Stockholm, Sweden., Di Molfetta G; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-43180, Mölndal, Sweden., Blennow K; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-43180, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, SE-43180, Mölndal, Sweden., Zetterberg H; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-43180, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, SE-43180, Mölndal, Sweden.; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.; UK Dementia Research Institute at UCL, London, WC1N 3BG, UK.; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53792, USA., Nordberg A; Department of Neurobiology, Care Sciences and Society, Centre for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, SE-14183, Stockholm, Sweden. agneta.k.nordberg@ki.se.; Theme Inflammation and Aging, Karolinska University Hospital, SE-14186, Stockholm, Sweden. agneta.k.nordberg@ki.se.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2023 Jul 25; Vol. 13 (1), pp. 268. Date of Electronic Publication: 2023 Jul 25.
DOI: 10.1038/s41398-023-02558-4
Abstrakt: Plasma biomarkers have shown promising performance in research cohorts in discriminating between different stages of Alzheimer's disease (AD). Studies in clinical populations are necessary to provide insights on the clinical utility of plasma biomarkers before their implementation in real-world settings. Here we investigated plasma biomarkers (glial fibrillary acidic protein (GFAP), tau phosphorylated at 181 and 231 (pTau181, pTau231), amyloid β (Aβ) 42/40 ratio, neurofilament light) in 126 patients (age = 65 ± 8) who were admitted to the Clinic for Cognitive Disorders, at Karolinska University Hospital. After extensive clinical assessment (including CSF analysis), patients were classified as: mild cognitive impairment (MCI) (n = 75), AD (n = 25), non-AD dementia (n = 16), no dementia (n = 9). To refine the diagnosis, patients were examined with [ 18 F]flutemetamol PET (Aβ-PET). Aβ-PET images were visually rated for positivity/negativity and quantified in Centiloid. Accordingly, 68 Aβ+ and 54 Aβ- patients were identified. Plasma biomarkers were measured using single molecule arrays (SIMOA). Receiver-operated curve (ROC) analyses were performed to detect Aβ-PET+ using the different biomarkers. In the whole cohort, the Aβ-PET centiloid values correlated positively with plasma GFAP, pTau231, pTau181, and negatively with Aβ42/40 ratio. While in the whole MCI group, only GFAP was associated with Aβ PET centiloid. In ROC analyses, among the standalone biomarkers, GFAP showed the highest area under the curve discriminating Aβ+ and Aβ- compared to other plasma biomarkers. The combination of plasma biomarkers via regression was the most predictive of Aβ-PET, especially in the MCI group (prior to PET, n = 75) (sensitivity = 100%, specificity = 82%, negative predictive value = 100%). In our cohort of memory clinic patients (mainly MCI), the combination of plasma biomarkers was sensitive in ruling out Aβ-PET negative individuals, thus suggesting a potential role as rule-out tool in clinical practice.
(© 2023. The Author(s).)
Databáze: MEDLINE
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