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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Ashton, Nicholas J., et al.
(författare)
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A plasma protein classifier for predicting amyloid burden for preclinical Alzheimer's disease.
- 2019
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- A blood-based assessment of preclinical disease would have huge potential in the enrichment of participants for Alzheimer's disease (AD) therapeutic trials. In this study, cognitively unimpaired individuals from the AIBL and KARVIAH cohorts were defined as Aβ negative or Aβ positive by positron emission tomography. Nontargeted proteomic analysis that incorporated peptide fractionation and high-resolution mass spectrometry quantified relative protein abundances in plasma samples from all participants. A protein classifier model was trained to predict Aβ-positive participants using feature selection and machine learning in AIBL and independently assessed in KARVIAH. A 12-feature model for predicting Aβ-positive participants was established and demonstrated high accuracy (testing area under the receiver operator characteristic curve = 0.891, sensitivity = 0.78, and specificity = 0.77). This extensive plasma proteomic study has unbiasedly highlighted putative and novel candidates for AD pathology that should be further validated with automated methodologies.
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| 3. |
- Chatterjee, Pratishtha, et al.
(författare)
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Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease.
- 2022
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 18:6, s. 1141-1154
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Tidskriftsartikel (refereegranskat)abstract
- This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t-tau), phosphorylated tau (p-tau181 and p-tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD).Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ-) or presence (Aβ+) of brain amyloidosis.Plasma GFAP, t-tau, p-tau181, and p-tau231 concentrations were higher in Aβ+ CU compared with Aβ- CU cross-sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aβ+ and Aβ- CU; however, no statistically significant differences were observed between the AUCs of GFAP, p-tau181, and p-tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t-tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene (APOE) ε4 status with GFAP was observed to have a higher AUC (>90%) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p-tau181 in Aβ+ CU and increased NFL in Aβ- CU, over a 12-month duration. GFAP, p-tau181, p-tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippocampal volume.These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p-tau for preclinical AD.
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| 4. |
- Dhiman, Kunal, et al.
(författare)
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Cerebrospinal fluid neurofilament light concentration predicts brain atrophy and cognition in Alzheimer's disease.
- 2020
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Ingår i: Alzheimer's & dementia (Amsterdam, Netherlands). - : Wiley. - 2352-8729. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- This study assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) in Alzheimer's disease (AD) diagnosis, its association with amyloid and tau pathology, as well as its potential to predict brain atrophy, cognition, and amyloid accumulation.CSF NfL concentration was measured in 221 participants from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL).CSF NfL levels as well as NfL/amyloid β (Aβ42) were significantly elevated in AD compared to healthy controls (HC; P < .001), and in mild cognitive impairment (MCI) compared to HC (P = .008 NfL; P < .001 NfL/Aβ42). CSF NfL and NfL/Aβ42 differentiated AD from HC with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.84 and 0.90, respectively. CSF NfL and NfL/Aβ42 predicted cortical amyloid load, brain atrophy, and cognition.CSF NfL is a biomarker of neurodegeneration, correlating with cognitive impairment and brain neuropathology.
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