Plasma Aβ but Not Tau is Related to Brain PiB Retention in Early Alzheimer’s Disease

Tzen, Kai-Yuan; Yang, Shieh Yueh; Chen, Ta Fu; Cheng, Ting Wen; Horng, Herng Er; Wen, Hsiang Ping; Huang, Ya-Yao; Shiue, Chyng‐Yann; Chiu, Ming‐Jang

doi:10.1021/cn500101j

Cited by 92 publications

(101 citation statements)

References 57 publications

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“…The small increase in patients with AD was similar to that in a previous study on another cohort, 7 while other studies failed to detect differences between CNs, patients with MCI, and patients with AD 9 or found reduced plasma tau in patients with AD compared with CNs, patients with MCI, 4 or those with vascular dementia. 5 One group used an immunomagnetic reduction assay for plasma tau 8 with high separation between CNs and patients with AD (sensitivity and specificity >90% 3,6,8 ). Those findings await replication by independent groups.…”

Section: Discussionmentioning

confidence: 99%

“…Previous smaller studies failed to find associations between plasma tau and CSF tau 7 or PET Aβ biomarkers. 6 …”

Section: Discussionmentioning

confidence: 99%

“…Most studies of plasma tau in AD have been small, including up to ≈150 participants, 3–8 with one study including 273 participants. 9 The results have been contradictory, showing clearly elevated levels in AD (several studies from one group 3,6,8 ), mild elevations in AD, 7 no difference between patients with AD and controls, 9 or reduced levels in AD. 4,5 …”

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confidence: 99%

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Plasma tau in Alzheimer disease

et al. 2016

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Objective:To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism.Methods:This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive healthy controls (n = 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284 participants were studied. Associations were tested between plasma tau and diagnosis, CSF biomarkers, MRI measures, 18fluorodeoxyglucose-PET, and cognition.Results:Higher plasma tau was associated with AD dementia, higher CSF tau, and lower CSF Aβ42, but the correlations were weak and differed between ADNI and BioFINDER. Longitudinal analysis in ADNI showed significant associations between plasma tau and worse cognition, more atrophy, and more hypometabolism during follow-up.Conclusions:Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia. Despite group-level differences, these results do not support plasma tau as an AD biomarker in individual people. Future studies may test longitudinal plasma tau measurements in AD.

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Section: Discussionmentioning

confidence: 99%

“…Previous smaller studies failed to find associations between plasma tau and CSF tau 7 or PET Aβ biomarkers. 6 …”

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Plasma tau in Alzheimer disease

et al. 2016

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“…SCD) may already occur in the stage of Aß42 accumulation in the absence of significant neurodegeneration 19 . Previous studies showed increased tau plasma levels in patients with AD [4][5][6] , in a group of patients with AD and mild cognitive impairment (MCI) due to AD 7 and in MCI due to AD 4 , but not in clinically classified MCI groups converting or not to AD during follow-up 5,6 . Taken together, our own result and these findings in literature indicate that plasma tau is a late marker of neurodegeneration, requiring substantial injury before increasing to abnormal levels at the transition from MCI to dementia stage of AD.…”

Section: Discussionmentioning

confidence: 97%

“…A blood test would fulfil all of these conditions in contrast to PET neuroimaging (expensive; exposure to ionizing radiation) and CSF analysis (invasive). Indeed, several previous studies have demonstrated increased tau plasma levels in patients with AD [4][5][6] , in a group of patients with AD and mild cognitive impairment (MCI) due to AD 7 and in MCI due to AD 4 . Much less is known whether increased tau plasma levels can already be detected in the pre-MCI stage of subjective cognitive decline (SCD).…”

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confidence: 99%

[P3–218]: Tau Plasma Levels in Subjective Cognitive Decline: Results From the Delcode Study

Laske

Preische

Goepfert

et al. 2017

Alzheimer's & Dementia

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Previous studies have demonstrated increased tau plasma levels in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) due to AD. Much less is known whether increased tau plasma levels can already be detected in the pre-MCI stage of subjective cognitive decline (SCD). In the present study we measured tau plasma levels in 111 SCD patients and 134 age-and gendermatched cognitively healthy controls participating in the DZNE (German Center for Neurodegenerative Diseases) longitudinal study on cognition and dementia (DELCODE). Tau plasma levels were measured using ultra-sensitive, single-molecule array (Simoa) technology. We found no significant different tau plasma levels in SCD (3.4 pg/ml) compared with healthy controls (3.6 pg/ml) after controlling for age, gender, and education (p = 0.137). In addition, tau plasma levels did not correlate with Aβ42 (r = 0.073; p = 0.634), tau (r = −0.179; p = 0.240), and p-tau181 (r = −0.208; p = 0.171) cerebrospinal fluid (CSF) levels in a subgroup of 45 SCD patients with available CSF. In conclusion, plasma tau is not increased in SCD patients. In addition, the lack of correlation between tau in plasma and CSF in the examined cohort suggests that tau levels are affected by different factors in both biofluids.Brain deposition of neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau is a hallmark of Alzheimer's disease (AD) pathology 1 . Several tau tracers for positron emission tomography (PET) imaging including 18F-TH523 have been developed over the past few years 2 . As in the brain itself, tau levels in the cerebrospinal fluid (CSF) were found to be increased in AD patients 3 . Therefore, CSF tau provides a useful marker of tau pathology. Several tau-based therapeutic approaches are currently investigated. Thus, detection of tau levels holds enormous potential for both early diagnosis of AD and monitoring of disease-modifying therapeutics.

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Amyloid‐β PET in Alzheimer's disease: A systematic review and Bayesian meta‐analysis

Ruan

Sun

2022

Brain and Behavior

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Background: In recent years, longitudinal studies of Alzheimer's disease (AD) have been successively concluded. Our aim is to determine the efficacy of amyloid-β (Aβ) PET in diagnosing AD and early prediction of mild cognitive impairment (MCI) converting to AD. By pooling studies from different centers to explore in-depth whether diagnostic performance varies by population type, radiotracer type, and diagnostic approach, thus providing a more comprehensive theoretical basis for the subsequent widespread application of Aβ PET in the clinical setting.Methods: Relevant studies were searched through PubMed. The pooled sensitivities, specificities, DOR, and the summary ROC curve were obtained based on a Bayesian random-effects model. Results:Forty-eight studies, including 5967 patients, were included. Overall, the pooled sensitivity, specificity, DOR, and AUC of Aβ PET for diagnosing AD were 0.90, 0.80, 35.68, and 0.91, respectively. Subgroup analysis showed that Aβ PET had high sensitivity (0.91) and specificity (0.81) for differentiating AD from normal controls but very poor specificity (0.49) for determining AD from MCI. The pooled sensitivity and specificity were 0.84 and 0.62, respectively, for predicting the conversion of MCI to AD. The differences in diagnostic efficacy between visual assessment and quantitative analysis and between 11 C-PIB PET and 18 F-florbetapir PET were insignificant. Conclusions:The overall performance of Aβ PET in diagnosing AD is favorable, but the differentiation between MCI and AD patients should consider that some MCI may be at risk of conversion to AD and may be misdiagnosed. A multimodal diagnostic approach and machine learning analysis may be effective in improving diagnostic accuracy.

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Plasma Aβ but Not Tau is Related to Brain PiB Retention in Early Alzheimer’s Disease

Cited by 92 publications

References 57 publications

Plasma tau in Alzheimer disease

Plasma tau in Alzheimer disease

[P3–218]: Tau Plasma Levels in Subjective Cognitive Decline: Results From the Delcode Study

Amyloid‐β PET in Alzheimer's disease: A systematic review and Bayesian meta‐analysis

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