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- Bucci, M., et al.
(författare)
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Profiling of plasma biomarkers in the context of memory assessment in a tertiary memory clinic
- 2023
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Ingår i: Translational Psychiatry. - 2158-3188. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- 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 & beta; (A & beta;) 42/40 ratio, neurofilament light) in 126 patients (age = 65 & PLUSMN; 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 [F-18]flutemetamol PET (A & beta;-PET). A & beta;-PET images were visually rated for positivity/negativity and quantified in Centiloid. Accordingly, 68 A & beta;+ and 54 A & beta;- patients were identified. Plasma biomarkers were measured using single molecule arrays (SIMOA). Receiver-operated curve (ROC) analyses were performed to detect A & beta;-PET+ using the different biomarkers. In the whole cohort, the A & beta;-PET centiloid values correlated positively with plasma GFAP, pTau231, pTau181, and negatively with A & beta;42/40 ratio. While in the whole MCI group, only GFAP was associated with A & beta; PET centiloid. In ROC analyses, among the standalone biomarkers, GFAP showed the highest area under the curve discriminating A & beta;+ and A & beta;- compared to other plasma biomarkers. The combination of plasma biomarkers via regression was the most predictive of A & beta;-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 A & beta;-PET negative individuals, thus suggesting a potential role as rule-out tool in clinical practice.
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| 2. |
- Chiotis, K., et al.
(författare)
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Tracking reactive astrogliosis in autosomal dominant and sporadic Alzheimer's disease with multi-modal PET and plasma GFAP
- 2023
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Ingår i: Molecular Neurodegeneration. - 1750-1326. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPlasma assays for the detection of Alzheimer's disease neuropathological changes are receiving ever increasing interest. The concentration of plasma glial fibrillary acidic protein (GFAP) has been suggested as a potential marker of astrocytes or recently, amyloid-& beta; burden, although this hypothesis remains unproven. We compared plasma GFAP levels with the astrocyte tracer 11C-Deuterium-L-Deprenyl (11C-DED) in a multi-modal PET design in participants with sporadic and Autosomal Dominant Alzheimer's disease.MethodsTwenty-four individuals from families with known Autosomal Dominant Alzheimer's Disease mutations (mutation carriers = 10; non-carriers = 14) and fifteen patients with sporadic Alzheimer's disease were included. The individuals underwent PET imaging with 11C-DED, 11C-PIB and 18F-FDG, as markers of reactive astrogliosis, amyloid-& beta; deposition, and glucose metabolism, respectively, and plasma sampling for measuring GFAP concentrations. Twenty-one participants from the Autosomal Dominant Alzheimer's Disease group underwent follow-up plasma sampling and ten of these participants underwent follow-up PET imaging.ResultsIn mutation carriers, plasma GFAP levels and 11C-PIB binding increased, while 11C-DED binding and 18F-FDG uptake significantly decreased across the estimated years to symptom onset. Cross-sectionally, plasma GFAP demonstrated a negative correlation with 11C-DED binding in both mutation carriers and patients with sporadic disease. Plasma GFAP indicated cross-sectionally a significant positive correlation with 11C-PIB binding and a significant negative correlation with 18F-FDG in the whole sample. The longitudinal levels of 11C-DED binding showed a significant negative correlation with longitudinal plasma GFAP concentrations over the follow-up interval.ConclusionsPlasma GFAP concentration and astrocyte 11C-DED brain binding levels followed divergent trajectories and may reflect different underlying processes. The strong negative association between plasma GFAP and 11C-DED binding in Autosomal Dominant and sporadic Alzheimer's disease brains may indicate that if both are markers of reactive astrogliosis, they may detect different states or subtypes of astrogliosis. Increased 11C-DED brain binding seems to be an earlier phenomenon in Alzheimer's disease progression than increased plasma GFAP concentration.
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| 4. |
- Oeckl, P., et al.
(författare)
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Blood beta-synuclein is related to amyloid PET positivity in memory clinic patients
- 2023
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 19:11, s. 4896-4907
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: beta-synuclein is an emerging blood biomarker to study synaptic degeneration in Alzheimert's disease (AD), but its relation to amyloid-beta (A beta) pathology is unclear. Methods: We investigated the association of plasma beta-synuclein levels with ([18F])flutemetamol positron emission tomography (PET) in patients with AD dementia (n = 51), mild cognitive impairment (MCI-A beta+ n = 18, MCI-A beta-n = 30), non-AD dementias (n = 22), and non-demented controls (n = 5). Results: Plasma beta-synuclein levels were higher in A beta+(AD dementia, MCI-A beta+) than in A beta-subjects (non-AD dementias, MCI-A beta-) with good discrimination of A beta+ from A beta-subjects and prediction of A beta status in MCI individuals. A positive correlation between plasma beta-synuclein and A beta PET was observed in multiple cortical regions across all lobes. Discussion: Plasma beta-synuclein demonstrated discriminative properties for A beta PET positive and negative subjects. Our data underline that beta-synuclein is not a direct marker of A beta pathology and suggest different longitudinal dynamics of synaptic degeneration versus amyloid deposition across the AD continuum.
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