Plasma tau/amyloid-β1–42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer’s disease

Park, Jong Chan; Han, Sun Ho; Yi, Dahyun; Byun, Min Soo; Lee, Jun Ho; Jang, Sukjin; Ko, Kang; Jeon, So Yeon; Lee, Yun Sang; Kim, Yu Kyeong; Lee, Dong Hoon; Mook‐Jung, Inhee

doi:10.1093/brain/awy347

Cited by 133 publications

(156 citation statements)

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“…Finally, this study was one of the first to show significant associations between plasma Aβ F42:F40 and Aβ T42:T40 and cerebral tau deposition on both regional and voxel‐wise analyses. These findings support recently reported findings showing that plasma t‐tau, p‐tau, and the ratios of t‐tau/Aβ42 and p‐tau/Aβ42 are associated with tau deposition on PET, as well as longitudinal changes in cerebral amyloid and neurodegeneration [37].…”

Section: Discussionsupporting

confidence: 92%

“…Another factor that may influence the relationship between plasma Aβ analyte levels and other outcomes is the role of genetic variation, particularly apolipoprotein E ( APOE ) [44]. Finally, a recent study also showed a significant association of the tau/Aβ42 ratio with tau PET in a largely cognitively normal (CN) Korean sample [37].…”

Section: Introductionmentioning

confidence: 99%

“…Reduced plasma Ab has also been linked to poorer cognition [6,7,19,21,[27][28][29][30]. In addition, some studies have suggested that plasma levels of Ab42 and Ab40 are associated with the levels of cerebral Ab on positron emission tomography (PET), cerebrospinal fluid levels of Ab and tau, and AD-like brain atrophy [4,7,8,11,16,17,24,[31][32][33][34][35][36][37][38], while others have not seen such an association [25,39,40]. These conflicting results may be due to the type of plasma markers measured and the methodologies used to extract these values.…”

Section: Introductionmentioning

confidence: 99%

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Plasma amyloid beta levels are associated with cerebral amyloid and tau deposition

Risacher

Fandos

Romero

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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Introduction We investigated the relationship of plasma amyloid beta (Aβ) with cerebral deposition of Aβ and tau on positron emission tomography (PET). Methods Forty-four participants (18 cognitively normal older adults [CN], 10 mild cognitive impairment, 16 Alzheimer's disease [AD]) underwent amyloid PET and a blood draw. Free and total plasma Aβ40 and Aβ42 were assessed using a validated assay. Thirty-seven participants (17 CN, 8 mild cognitive impairment, 12 AD) also underwent a [ 18 F]flortaucipir scan. Scans were preprocessed by standard techniques, and mean global and regional amyloid and tau values were extracted. Free Aβ42/Aβ40 (Aβ F42:F40) and total Aβ42/Aβ40 (Aβ T42:T40) were evaluated for differences by diagnosis and relation to PET Aβ positivity. Relationships between these measures and cerebral Aβ and tau on both regional and voxel-wise basis were also evaluated. Results Lower Aβ T42:T40 was associated with diagnosis and PET Aβ positivity. Lower plasma Aβ T42:T40 ratios predicted cerebral Aβ positivity, both across the full sample and in CN only. Finally, lower plasma Aβ T42:T40 ratios were associated with increased cortical Aβ and tau in AD-related regions on both regional and voxel-wise analyses. Discussion Plasma Aβ measures may be useful biomarkers for predicting cerebral Aβ and tau. Additional studies in larger samples are warranted.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Plasma amyloid beta levels are associated with cerebral amyloid and tau deposition

Risacher

Fandos

Romero

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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“…In addition, the estimated average concentration of Aβ 42 in AD patients' blood plasma was 2.97 times higher than in normal controls (p < 0.001, one-way ANOVA), whereas the level of Aβ 40 in plasma was similar for both groups (p = 0.26, one-way ANOVA). The measured plasma levels of AD biomarkers are listed in Supplementary Table 4, which are comparable to the reported values in previous clinical studies 11,12,24,25 . It is noteworthy that our sensor array could detect both unbound Aβ 42 and Aβ 42 bound with other proteins in blood plasma, because the resistance of our sensor array increased upon exposure to the plasma filtrate as well as to the native plasma sample ( Supplementary Fig.…”

Section: Multiplex Sensing Of Ad Biomarkers In Clinical Blood Samplessupporting

confidence: 82%

“…Clinical studies have reported that the concentration of t-tau protein in AD patients' cerebrospinal fluid (CSF) is two to three times higher than that of normal controls, whereas Aβ 42 decreases by~40% in AD patients when compared with those of healthy individuals 10 . Recently, a strong correlation between the levels of AD biomarkers in blood plasma and pathological changes in the brain have been reported 11,12 . As the CSF sampling process via lumbar puncture has serious drawbacks, including invasiveness and lack of accessibility 13 , well-validated blood-based biomarker panels may facilitate minimally invasive assessment of AD patients in primary care settings and continuous monitoring of disease progression.…”

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confidence: 99%

Clinically accurate diagnosis of Alzheimer’s disease via multiplexed sensing of core biomarkers in human plasma

et al. 2020

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Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, affecting one in ten people aged over 65 years. Despite the severity of the disease, early diagnosis of AD is still challenging due to the low accuracy or high cost of neuropsychological tests and neuroimaging. Here we report clinically accurate and ultrasensitive detection of multiple AD core biomarkers (t-tau, p-tau 181 , Aβ 42 , and Aβ 40) in human plasma using densely aligned carbon nanotubes (CNTs). The closely packed and unidirectionally aligned CNT sensor array exhibits high precision, sensitivity, and accuracy, evidenced by a low coefficient of variation (<6%), a femtomolar-level limit of detection, and a high degree of recovery (>93.0%). By measuring the levels of t-tau/Aβ 42 , p-tau 181 /Aβ 42 , and Aβ 42 /Aβ 40 in clinical blood samples, the sensor array successfully discriminates the clinically diagnosed AD patients from healthy controls with an average sensitivity of 90.0%, a selectivity of 90.0%, and an average accuracy of 88.6%.

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Plasma Leptin and Alzheimer Protein Pathologies Among Older Adults

Lee,

Byun,

et al. 2024

JAMA Netw Open

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ImportanceMany epidemiologic studies have suggested that low levels of plasma leptin, a major adipokine, are associated with increased risk of Alzheimer disease (AD) dementia and cognitive decline. Nevertheless, the mechanistic pathway linking plasma leptin and AD-related cognitive decline is not yet fully understood.ObjectiveTo examine the association of plasma leptin levels with in vivo AD pathologies, including amyloid-beta (Aβ) and tau deposition, through both cross-sectional and longitudinal approaches among cognitively unimpaired older adults.Design, Setting, and ParticipantsThis was a longitudinal cohort study from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer Disease. Data were collected from January 1, 2014, to December 31, 2020, and data were analyzed from July 11 to September 6, 2022. The study included a total of 208 cognitively unimpaired participants who underwent baseline positron emission tomography (PET) scans for brain Aβ deposition. For longitudinal analyses, 192 participants who completed both baseline and 2-year follow-up PET scans for brain Aβ deposition were included.ExposurePlasma leptin levels as assessed by enzyme-linked immunosorbent assay.Main Outcomes and MeasuresBaseline levels and longitudinal changes of global Aβ and AD-signature region tau deposition measured by PET scans.ResultsAmong the 208 participants, the mean (SD) age was 66.0 (11.3) years, 114 were women (54.8%), and 37 were apolipoprotein E ε4 carriers (17.8%). Lower plasma leptin levels had a significant cross-sectional association with greater brain Aβ deposition (β = −0.04; 95% CI, −0.09 to 0.00; P = .046), while there was no significant association between plasma leptin levels and tau deposition (β = −0.02; 95% CI, −0.05 to 0.02; P = .41). In contrast, longitudinal analyses revealed that there was a significant association between lower baseline leptin levels and greater increase of tau deposition over 2 years (β = −0.06; 95% CI, −0.11 to −0.01; P = .03), whereas plasma leptin levels did not have a significant association with longitudinal change of Aβ deposition (β = 0.006; 95% CI, 0.00-0.02; P = .27).Conclusions and RelevanceThe present findings suggest that plasma leptin may be protective for the development or progression of AD pathology, including both Aβ and tau deposition.

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Plasma tau/amyloid-β1–42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer’s disease

Cited by 133 publications

References 67 publications

Plasma amyloid beta levels are associated with cerebral amyloid and tau deposition

Plasma amyloid beta levels are associated with cerebral amyloid and tau deposition

Clinically accurate diagnosis of Alzheimer’s disease via multiplexed sensing of core biomarkers in human plasma

Plasma Leptin and Alzheimer Protein Pathologies Among Older Adults

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