Association of plasma biomarkers of amyloid and neurodegeneration with cerebrovascular disease and Alzheimer's disease

Graff‐Radford, Jonathan; Mielke, Michelle M.; Hofrenning, Ekaterina I.; Kouri, Naomi; Lesnick, Timothy G.; Moloney, Christina M.; Rabinstein, Alejandro A.; Cabrera‐Rodriguez, Janisse N; Rothberg, Darren M; Przybelski, Scott A.; Petersen, Ronald C.; Knopman, David S.; Dickson, Dennis W.; Jack, Clifford R.; Algeciras‐Schimnich, Alicia; Nguyen, Aivi T.; Murray, Melissa E.; Vemuri, Prashanthi

doi:10.1016/j.neurobiolaging.2022.07.006

Cited by 6 publications

(9 citation statements)

References 32 publications

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“…Indeed, plasma A␤ levels may reflect only to some extent the A␤ aggregation in the brain due to peripheral A␤ generation, degradation by circulating enzymes, and metabolism in the liver [45]. In addition, the available A␤ assay was specific for x-40 and x-42 rather than 1-40 and 1-42, which was less disease-specific [46], and the head-to-head study showed that certain mass spectroscopy-based methods performed better than immunoassays for plasma A␤ 42 /A␤ 40 ratio when detecting A␤ pathology in the brain [47]. Plasma t-tau is considered a biomarker of neuronal damage and neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

Plasma Amyloid-β, Total Tau, and Neurofilament Light Chain Across the Alzheimer’s Disease Clinical Spectrum: A Population-Based Study

Dong,

Hou,

et al. 2023

JAD

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Background: Plasma biomarkers have emerged as a promising approach for characterizing pathophysiology in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Objective: We aimed to characterize plasma biomarkers for AD and neurodegeneration across the AD clinical continuum, and to assess their ability to differentiate between AD, MCI, and normal cognition. Methods: This population-based study engaged 1,446 rural-dwelling older adults (age ≥60 years, 61.0% women) derived from MIND-China; of these, 402 were defined with MCI and 142 with AD. Plasma amyloid-β (Aβ), total tau (t-tau), and neurofilament light chain (NfL) concentrations were analyzed using the Simoa platform. Data were analyzed using linear and logistic regression models, and receiver operating characteristic (ROC) analysis. Results: Across the AD clinical spectrum, plasma Aβ40 and NfL increased, whereas Aβ42/Aβ40 ratio decreased. Plasma t-tau was higher in people with AD dementia than those with MCI or normal cognition. Plasma NfL outperformed other biomarkers in differentiating AD from normal cognition (area under the ROC curve [AUC] = 0.75), but all plasma biomarkers performed poorly to distinguish MCI from normal cognition (AUC <0.60). Plasma NfL in combination with age, sex, education, and APOE genotype yielded the AUC of 0.87 for differentiating between AD and normal cognition, 0.79 between AD and MCI, and 0.64 between MCI and normal cognition. Conclusions: In this Chinese population, AD plasma biomarkers vary by age, sex, and APOE genotype. Plasma Aβ, t-tau, and NfL differ across the AD clinical spectrum, and plasma NfL appears to be superior to plasma Aβ and t-tau for defining the clinical spectrum.

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Section: Discussionmentioning

confidence: 99%

Plasma Amyloid-β, Total Tau, and Neurofilament Light Chain Across the Alzheimer’s Disease Clinical Spectrum: A Population-Based Study

Dong,

Hou,

et al. 2023

JAD

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“…These altogether conflicting results suggest a non‐linear relationship between age, trisomy 21, and plaque deposition, rendering plasma Aβ alone unlikely to be a useful biomarker in the DS population. Other possible contributors to variability in plasma Aβ with disease progression in DS may reflect the development of cerebral amyloid angiopathy, leading to additional and perhaps variable leakage of Aβ into the bloodstream 31 . Although people with DS show more extensive cerebral amyloid angiopathy at autopsy and in vivo observed by MRI than cases with late onset AD, there can be individual variability in the extent and location of these changes 32,33 …”

Section: Discussionmentioning

confidence: 99%

“…Other possible contributors to variability in plasma Aβ with disease progression in DS may reflect the development of cerebral amyloid angiopathy, leading to additional and perhaps variable leakage of Aβ into the bloodstream. 31 Although people with DS show more extensive cerebral amyloid angiopathy at autopsy and in vivo observed by MRI than cases with late onset AD, there can be individual variability in the extent and location of these changes. 32,33 The variable measures across timepoints within individuals (Figure S1) is important to consider for NT1-tau, but also other plasma biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Plasma NT1‐tau and Aβ₄₂ correlate with age and cognitive function in two large Down syndrome cohorts

Stern

Pelt

Liu

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONPeople with Down syndrome (DS) often develop Alzheimer's disease (AD). Here, we asked whether ultrasensitive plasma immunoassays for a tau N‐terminal fragment (NT1‐tau) and Aβ isoforms predict cognitive impairment.METHODSPlasma NT1‐tau, Aβ37, Aβ40, and Aβ42 levels were measured in a longitudinal discovery cohort (N = 85 participants, 220 samples) and a cross‐sectional validation cohort (N = 239). We developed linear models and predicted values in the validation cohort.RESULTSDiscovery cohort linear mixed models for NT1‐tau, Aβ42, and Aβ37:42 were significant for age; there was no main effect of time. In cross‐sectional models, NT1‐tau increased and Aβ42 decreased with age. NT1‐tau predicted cognitive and functional scores. The discovery cohort linear model for NT1‐tau predicted levels in the validation cohort.DISCUSSIONNT1‐tau correlates with age and worse cognition in DS. Further validation of NT1‐tau and other plasma biomarkers of AD neuropathology in DS cohorts is important for clinical utility.

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“…The detailed description of plasma collection, as well as NfL and GFAP measurements, were published previously. [32][33][34][35] The participant's blood was collected at a MCSA clinic visit after overnight fasting.…”

Section: Plasma Measuresmentioning

confidence: 99%

Vascular risk, gait, behavioral, and plasma indicators of VCID

Raghavan,

Przybelski,

Lesnick

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONCost‐effective screening tools for vascular contributions to cognitive impairment and dementia (VCID) has significant implications. We evaluated non‐imaging indicators of VCID using magnetic resonance imaging (MRI)‐measured white matter (WM) damage and hypothesized that these indicators differ based on age.METHODSIn 745 participants from the Mayo Clinic Study of Aging (≥50 years of age) with serial WM assessments from diffusion MRI and fluid‐attenuated inversion recovery (FLAIR)‐MRI, we examined associations between baseline non‐imaging indicators (demographics, vascular risk factors [VRFs], gait, behavioral, plasma glial fibrillary acidic protein [GFAP], and plasma neurofilament light chain [NfL]) and WM damage across three age tertiles.RESULTSVRFs and gait were associated with diffusion changes even in low age strata. All measures (VRFs, gait, behavioral, plasma GFAP, plasma NfL) were associated with white matter hyperintensities (WMHs) but mainly in intermediate and high age strata.DISCUSSIONNon‐imaging indicators of VCID were related to WM damage and may aid in screening participants and assessing outcomes for VCID.HIGHLIGHTS Non‐imaging indicators of VCID can aid in prediction of MRI‐measured WM damage but their importance differed by age. Vascular risk and gait measures were associated with early VCID changes measured using diffusion MRI. Plasma markers explained variability in WMH across age strata. Most non‐imaging measures explained variability in WMH and vascular WM scores in intermediate and older age groups. The framework developed here can be used to evaluate new non‐imaging VCID indicators proposed in the future.

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Association of plasma biomarkers of amyloid and neurodegeneration with cerebrovascular disease and Alzheimer's disease

Cited by 6 publications

References 32 publications

Plasma Amyloid-β, Total Tau, and Neurofilament Light Chain Across the Alzheimer’s Disease Clinical Spectrum: A Population-Based Study

Plasma Amyloid-β, Total Tau, and Neurofilament Light Chain Across the Alzheimer’s Disease Clinical Spectrum: A Population-Based Study

Plasma NT1‐tau and Aβ₄₂ correlate with age and cognitive function in two large Down syndrome cohorts

Vascular risk, gait, behavioral, and plasma indicators of VCID

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Association of plasma biomarkers of amyloid and neurodegeneration with cerebrovascular disease and Alzheimer's disease

Cited by 6 publications

References 32 publications

Plasma Amyloid-β, Total Tau, and Neurofilament Light Chain Across the Alzheimer’s Disease Clinical Spectrum: A Population-Based Study

Plasma Amyloid-β, Total Tau, and Neurofilament Light Chain Across the Alzheimer’s Disease Clinical Spectrum: A Population-Based Study

Plasma NT1‐tau and Aβ42 correlate with age and cognitive function in two large Down syndrome cohorts

Vascular risk, gait, behavioral, and plasma indicators of VCID

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Plasma NT1‐tau and Aβ₄₂ correlate with age and cognitive function in two large Down syndrome cohorts