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- Huber, Hanna, 1989, et al.
(författare)
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Biomarkers of Alzheimer's disease and neurodegeneration in dried blood spots-A new collection method for remote settings
- 2024
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Ingår i: ALZHEIMERS & DEMENTIA. - 1552-5260 .- 1552-5279.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We aimed to evaluate the precision of Alzheimer's disease (AD) and neurodegeneration biomarker measurements from venous dried plasma spots (DPSvenous) for the diagnosis and monitoring of neurodegenerative diseases in remote settings. METHODS: In a discovery (n = 154) and a validation cohort (n = 115), glial fibrillary acidic protein (GFAP); neurofilament light (NfL); amyloid beta (A beta) 40, A beta 42; and phosphorylated tau (p-tau181 and p-tau217) were measured in paired DPSvenous and ethylenediaminetetraacetic acid plasma samples with single-molecule array. In the validation cohort, a subset of participants (n = 99) had cerebrospinal fluid (CSF) biomarkers. RESULTS: All DPSvenous and plasma analytes correlated significantly, except for A beta 42. In the validation cohort, DPSvenous GFAP, NfL, p-tau181, and p-tau217 differed between CSF A beta-positive and -negative individuals and were associated with worsening cognition. DISCUSSION: Our data suggest that measuring blood biomarkers related to AD pathology and neurodegeneration from DPSvenous extends the utility of blood-based biomarkers to remote settings with simplified sampling conditions, storage, and logistics.
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| 2. |
- Huber, Hanna, 1989, et al.
(författare)
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Levels of Alzheimer's disease blood biomarkers are altered after food intake-A pilot intervention study in healthy adults
- 2023
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 19:12, s. 5531-5540
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONBlood biomarkers accurately identify Alzheimer's disease (AD) pathophysiology and axonal injury. We investigated the influence of food intake on AD-related biomarkers in cognitively healthy, obese adults at high metabolic risk. METHODSOne-hundred eleven participants underwent repeated blood sampling during 3 h after a standardized meal (postprandial group, PG). For comparison, blood was sampled from a fasting subgroup over 3 h (fasting group, FG). Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), amyloid-beta (A beta) 42/40, phosphorylated tau (p-tau) 181 and 231, and total-tau were measured via single molecule array assays. RESULTSSignificant differences were found for NfL, GFAP, A beta 42/40, p-tau181, and p-tau231 between FG and PG. The greatest change to baseline occurred for GFAP and p-tau181 (120 min postprandially, p < 0.0001). CONCLUSIONOur data suggest that AD-related biomarkers are altered by food intake. Further studies are needed to verify whether blood biomarker sampling should be performed in the fasting state. HighlightsAcute food intake alters plasma biomarkers of Alzheimer's disease in obese, otherwise healthy adults.We also found dynamic fluctuations in plasma biomarkers concentration in the fasting state suggesting physiological diurnal variations.Further investigations are highly needed to verify if biomarker measurements should be performed in the fasting state and at a standardized time of day to improve the diagnostic accuracy.
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| 3. |
- Kolanko, Magdalena A., et al.
(författare)
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Quantification of neurofilament light and glial fibrillary acidic protein in finger-prick blood
- 2024
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Ingår i: BRAIN COMMUNICATIONS. - 2632-1297. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- An accurate diagnosis of neurodegenerative disease and traumatic brain injury is important for prognostication and treatment. Neurofilament light and glial fibrillary acidic protein (GFAP) are leading biomarkers for neurodegeneration and glial activation that are detectable in blood. Yet, current recommendations require rapid centrifugation and ultra-low temperature storage post-venepuncture. Here, we investigated if these markers can be accurately measured in finger-prick blood using dried plasma spot cards. Fifty patients (46 with dementia; 4 with traumatic brain injury) and 19 healthy volunteers underwent finger-prick and venous sampling using dried plasma spot cards and aligned plasma sampling. Neurofilament light and GFAP were quantified using a Single molecule array assay and correlations between plasma and dried plasma spot cards assessed. Biomarker concentrations in plasma and finger-prick dried plasma spot samples were significantly positively correlated (neurofilament light rho = 0.57; GFAP rho = 0.58, P < 0.001). Finger-prick neurofilament light and GFAP were significantly elevated after acute traumatic brain injury with non-significant group-level increases in dementia (91% having Alzheimer's disease dementia). In conclusion, we present preliminary evidence that quantifying GFAP and neurofilament light using finger-prick blood collection is viable, with samples stored at room temperature using dried plasma spot cards. This has potential to expand and promote equitable testing access, including in settings where trained personnel are unavailable to perform venepuncture.
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| 4. |
- Lantero Rodriguez, Juan, et al.
(författare)
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CSF p-tau205: a biomarker of tau pathology in Alzheimer's disease.
- 2024
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Ingår i: Acta neuropathologica. - 1432-0533. ; 147:1
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Tidskriftsartikel (refereegranskat)abstract
- Post-mortem staging of Alzheimer's disease (AD) neurofibrillary pathology is commonly performed by immunohistochemistry using AT8 antibody for phosphorylated tau (p-tau) at positions 202/205. Thus, quantification of p-tau205 and p-tau202 in cerebrospinal fluid (CSF) should be more reflective of neurofibrillary tangles in AD than other p-tau epitopes. We developed two novel Simoa immunoassays for CSF p-tau205 and p-tau202 and measured these phosphorylations in three independent cohorts encompassing the AD continuum, non-AD cases and cognitively unimpaired participants: a discovery cohort (n=47), an unselected clinical cohort (n=212) and a research cohort well-characterized by fluid and imaging biomarkers (n=262). CSF p-tau205 increased progressively across the AD continuum, while CSF p-tau202 was increased only in AD and amyloid(Aβ) and tau pathology positive (A+T+) cases (P<0.01). In A+cases, CSF p-tau205 and p-tau202 showed stronger associations with tau-PET (rSp205=0.67, rSp202=0.45) than Aβ-PET (rSp205=0.40, rSp202=0.09). CSF p-tau205 increased gradually across tau-PET Braak stages (P<0.01), whereas p-tau202 only increased in Braak V-VI (P<0.0001). Both showed stronger regional associations with tau-PET than with Aβ-PET, and CSF p-tau205 was significantly associated with Braak V-VI tau-PET regions. When assessing the contribution of Aβ and tau pathologies (indexed by PET) to CSF p-tau205 and p-tau202 variance, tau pathology was found to be the most prominent contributor in both cases (CSF p-tau205: R2=69.7%; CSF p-tau202: R2=85.6%) Both biomarkers associated with brain atrophy measurements globally (rSp205=-0.36, rSp202=-0.33) and regionally, and correlated with cognition (rSp205=-0.38/-0.40, rSp202=-0.20/-0.29). In conclusion, we report the first high-throughput CSF p-tau205 immunoassay for the in vivo quantification of tau pathology in AD, and a potentially cost-effective alternative to tau-PET in clinical settings and clinical trials.
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