scholarly journals Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET

2020 ◽  
Vol 12 (524) ◽  
pp. eaau5732 ◽  
Author(s):  
Renaud La Joie ◽  
Adrienne V. Visani ◽  
Suzanne L. Baker ◽  
Jesse A. Brown ◽  
Viktoriya Bourakova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Pet ◽  
Specific Distribution ◽  
Positron Emission ◽  
Pet Radiotracers ◽  
Β Amyloid ◽  
Tau Pet ◽  
Prospective Longitudinal

β-Amyloid plaques and tau-containing neurofibrillary tangles are the two neuropathological hallmarks of Alzheimer’s disease (AD) and are thought to play crucial roles in a neurodegenerative cascade leading to dementia. Both lesions can now be visualized in vivo using positron emission tomography (PET) radiotracers, opening new opportunities to study disease mechanisms and improve patients’ diagnostic and prognostic evaluation. In a group of 32 patients at early symptomatic AD stages, we tested whether β-amyloid and tau-PET could predict subsequent brain atrophy measured using longitudinal magnetic resonance imaging acquired at the time of PET and 15 months later. Quantitative analyses showed that the global intensity of tau-PET, but not β-amyloid–PET, signal predicted the rate of subsequent atrophy, independent of baseline cortical thickness. Additional investigations demonstrated that the specific distribution of tau-PET signal was a strong indicator of the topography of future atrophy at the single patient level and that the relationship between baseline tau-PET and subsequent atrophy was particularly strong in younger patients. These data support disease models in which tau pathology is a major driver of local neurodegeneration and highlight the relevance of tau-PET as a precision medicine tool to help predict individual patient’s progression and design future clinical trials.

scholarly journals Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau

2021 ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Shorena Janelidze ◽  
Randall Bateman ◽  
Ruben Smith ◽  
Erik Stomrud ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medial Temporal Lobe ◽  
Amyloid Plaques ◽  
Amyloid Plaque ◽  
Amyloid Pet ◽  
Tau Pathology ◽  
Β Amyloid ◽  
Tau Pet ◽  
Disease Stages

Abstract Alzheimer’s disease is characterized by β-amyloid plaques and tau tangles. Plasma levels of phospho-tau217 (P-tau217) accurately differentiate Alzheimer’s disease dementia from other dementias, but it is unclear to what degree this reflects β-amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post-mortem neuropathological data (N=88), both plaque and tangle density contributed independently to higher P-tau217. Several findings were replicated in a cohort with PET imaging (“BioFINDER-2”, N=426), where β-amyloid and tau PET were independently associated to P-tau217. P-tau217 correlated with β-amyloid PET (but not tau PET) in early disease stages, and with both β-amyloid and (more strongly) tau PET in late disease stages. Finally, P-tau217 mediated the association between β-amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe. These findings support the hypothesis that plasma P-tau217 is increased by both β-amyloid plaques and tau tangles and is congruent with the hypothesis that P-tau is involved in β-amyloid-dependent formation of neocortical tau tangles.

scholarly journals Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer’s disease

2020 ◽  
Vol 6 (16) ◽  
pp. eaaz2387 ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Emelie Andersson ◽  
Shorena Janelidze ◽  
Rik Ossenkoppele ◽  
Philip Insel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Pet ◽  
Phosphorylated Tau ◽  
Positron Emission ◽  
Aβ Aggregation ◽  
Tau Pet ◽  
5Xfad Mice ◽  
Tau Aggregation ◽  
T Tau

The links between β-amyloid (Aβ) and tau in Alzheimer’s disease are unclear. Cognitively unimpaired persons with signs of Aβ pathology had increased cerebrospinal fluid (CSF) phosphorylated tau (P-tau181 and P-tau217) and total-tau (T-tau), which increased over time, despite no detection of insoluble tau aggregates [normal Tau positron emission tomography (PET)]. CSF P-tau and T-tau started to increase before the threshold for Amyloid PET positivity, while Tau PET started to increase after Amyloid PET positivity. Effects of Amyloid PET on Tau PET were mediated by CSF P-tau, and high CSF P-tau predicted increased Tau PET rates. Individuals with MAPT mutations and signs of tau deposition (but without Aβ pathology) had normal CSF P-tau levels. In 5xFAD mice, CSF tau increased when Aβ aggregation started. These results show that Aβ pathology may induce changes in soluble tau release and phosphorylation, which is followed by tau aggregation several years later in humans.

Amyloid imaging in Alzheimer’s disease: a potential new era of personalized medicine?

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Antoine Leuzy ◽  
Eduardo Zimmer ◽  
Serge Gauthier ◽  
Pedro Rosa-Neto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Personalized Medicine ◽  
Amyloid Imaging ◽  
Phase Iii ◽  
Diagnostic Process ◽  
European Medicines Agency ◽  
Amyloid Pet ◽  
Positron Emission

AbstractRecent advances along clinical and neuropathological lines, as well as in our ability to detect the deposition of β-amyloid (Aβ) in vivo using positron emission tomography (PET), have helped redefine Alzheimer’s disease (AD) as a dynamic clinicobiological entity. On the basis of these advances, AD is now conceptualized as a continuum comprising asymptomatic, minimally symptomatic, and dementia phases, with detection of brain Aβ — in particular, via PET amyloid imaging — central to the diagnostic process. In this respect, [18F]florbetapir (Amyvid™) and [18F]flutemetamol (Vizamyl™) have recently received approval for clinical use from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), with additional radiofluorinated tracers for detection of Aβ in phase III trials. Recent initiatives such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) suggest that Aβ production, oligomerization and aggregation begins many years, possibly decades, before detectable cognitive impairment, with Aβ shown to associate with cognitive decline and conversion to dementia. While personalized medicine has now emerged as a prospect for the field, the recent decision by the Centers for Medicare & Medicaid Services (CMS) — who declined to cover the cost of amyloid PET imaging citing insufficient evidence to support its clinical utility — highlights that such a move may be premature.

Elevated Tau PET Signal Depends on Abnormal Amyloid Levels and Correlates with Cognitive Impairment in Elderly Persons without Dementia

2020 ◽  
Vol 78 (1) ◽  
pp. 395-404 ◽  
Author(s):  
Rui-Qi Zhang ◽  
Shi-Dong Chen ◽  
Xue-Ning Shen ◽  
Yu-Xiang Yang ◽  
Jia-Ying Lu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
Amyloid Β ◽  
Amyloid Pet ◽  
Elderly Persons ◽  
Cross Sectional ◽  
Memory Decline ◽  
Tau Pet

Background: The recent developed PET ligands for amyloid-β (Aβ) and tau allow these two neuropathological hallmarks of Alzheimer’s disease (AD) to be mapped and quantified in vivo and to be examined in relation to cognition. Objective: To assess the associations among Aβ, tau, and cognition in non-demented subjects. Methods: Three hundred eighty-nine elderly participants without dementia from the Alzheimer’s Disease Neuroimaging Initiative underwent tau and amyloid PET scans. Cross-sectional comparisons and longitudinal analyses were used to evaluate the relationship between Aβ and tau accumulation. The correlations between biomarkers of both pathologies and performance in memory and executive function were measured. Results: Increased amyloid-PET retention was associated with greater tau-PET retention in widespread cortices. We observed a significant tau increase in the temporal composite regions of interest over 24 months in Aβ+ but not Aβ– subjects. Finally, tau-PET retention but not amyloid-PET retention significantly explained the variance in memory and executive function. Higher level of tau was associated with greater longitudinal memory decline. Conclusion: These findings suggested PET-detectable Aβ plaque pathology may be a necessary antecedent for tau-PET signal elevation. Greater tau-PET retention may demonstrate poorer cognition and predict prospective memory decline in non-demented subjects.

PET Amyloid and Tau Status Are Differently Affected by Patient Features

2020 ◽  
Vol 78 (3) ◽  
pp. 1129-1136
Author(s):  
Meng-Shan Tan ◽  
Yu-Xiang Yang ◽  
Hui-Fu Wang ◽  
Wei Xu ◽  
Chen-Chen Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Pet ◽  
Tau Pathology ◽  
Clinical Genetic ◽  
Multivariable Logistic Regression Model ◽  
Tau Pet ◽  
Pet Amyloid

Background: Amyloid-β (Aβ) plaques and tau neurofibrillary tangles are two neuropathological hallmarks of Alzheimer’s disease (AD), which both can be visualized in vivo using PET radiotracers, opening new opportunities to study disease mechanisms. Objective: Our study investigated 11 non-PET factors in 5 categories (including demographic, clinical, genetic, MRI, and cerebrospinal fluid (CSF) features) possibly affecting PET amyloid and tau status to explore the relationships between amyloid and tau pathology, and whether these features had a different association with amyloid and tau status. Methods: We included 372 nondemented elderly from the Alzheimer’s Disease Neuroimaging Initiative cohort. All underwent PET amyloid and tau analysis simultaneously, and were grouped into amyloid/tau quadrants based on previously established abnormality cut points. We examined the associations of above selected features with PET amyloid and tau status using a multivariable logistic regression model, then explored whether there was an obvious correlation between the significant features and PET amyloid or tau levels. Results: Our results demonstrated that PET amyloid and tau status were differently affected by patient features, and CSF biomarker features provided most significant values associating PET findings. CSF Aβ42/40 was the most important factor affecting amyloid PET status, and negatively correlated with amyloid PET levels. CSF pTau could significantly influence both amyloid and tau PET status. Besides CSF pTau and Aβ42, APOE ɛ4 allele status and Mini-Mental State Examination scores also could influence tau PET status, and significantly correlated with tau PET levels. Conclusion: Our results support that tau pathology possibly affected by Aβ-independent factors, implicating the importance of tau pathology in AD pathogenesis.

O1-02-07: In vivo characterization of 18F-BAY94-9172: A novel β-amyloid PET ligand for the diagnosis of Alzheimer's disease

2008 ◽  
Vol 4 ◽  
pp. T111-T111
Author(s):  
Christopher C. Rowe ◽  
Uwe Ackermann ◽  
Rachel S. Mulligan ◽  
Tim H. Saunder ◽  
Graeme O'Keefe ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Pet ◽  
Β Amyloid ◽  
In Vivo Characterization

scholarly journals Soluble P-tau217 reflects both amyloid and tau pathology in the human brain and mediates the association of amyloid with neocortical tau

2020 ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Shorena Janelidze ◽  
Randall Bateman ◽  
Ruben Smith ◽  
Erik Stomrud ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medial Temporal Lobe ◽  
Amyloid Plaques ◽  
Amyloid Plaque ◽  
Amyloid Pet ◽  
Tau Pathology ◽  
Β Amyloid ◽  
Tau Pet ◽  
Disease Stages

Abstract Alzheimer’s disease is characterized by β-amyloid plaques and tau tangles. Plasma levels of phospho-tau217 (P-tau217) accurately differentiate Alzheimer’s disease dementia from other dementias, but it is unclear to what degree this reflects β-amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post-mortem neuropathological data (N=88), both plaque and tangle density contributed independently to higher P-tau217. Several findings were replicated in a cohort with PET imaging (“BioFINDER-2”, N=426), where β-amyloid and tau PET were independently associated to P-tau217. P-tau217 correlated with β-amyloid PET (but not tau PET) in early disease stages, and with both β-amyloid and (more strongly) tau PET in late disease stages. Finally, P-tau217 mediated the association between β-amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe. These findings support the hypothesis that plasma P-tau217 is increased by both β-amyloid plaques and tau tangles and is congruent with the hypothesis that P-tau is involved in β-amyloid-dependent formation of neocortical tau tangles.

scholarly journals Towards harmonizing subtyping methods for neuroimaging studies in Alzheimer’s disease

2020 ◽  
Author(s):  
Rosaleena Mohanty ◽  
Gustav Mårtensson ◽  
Konstantinos Poulakis ◽  
J-Sebastian Muehlboeck ◽  
Elena Rodriguez-Vieitez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Reference Group ◽  
Group Level ◽  
Individual Level ◽  
Dementia Patients ◽  
Positron Emission ◽  
Tau Pet ◽  
The Individual

ABSTRACTBackgroundBiological subtypes in Alzheimer’s disease (AD), originally identified on neuropathological data, have been translated to in vivo biomarkers such as structural magnetic resonance imaging (sMRI) and positron emission tomography (PET), to disentangle the heterogeneity within AD. Although there is methodological variability across studies, comparable characteristics of subtypes are reported at the group level. In this study, we investigated whether group-level similarities translate to individual-level agreement across subtyping methods, in a head-to-head context.MethodsWe compared five previously published subtyping methods. Firstly, we validated the subtyping methods in 89 amyloid-beta positive (Aβ+) AD dementia patients (reference group: 70 Aβ-healthy individuals; HC) using sMRI. Secondly, we extended and applied the subtyping methods to 53 Aβ+ prodromal AD and 30 Aβ+ AD dementia patients (reference group: 200 Aβ-HC) using both sMRI and tau PET. Subtyping methods were implemented as outlined in each original study. Group-level and individual-level comparisons across methods were performed.ResultsEach individual method was replicated and the proof-of-concept was established. All methods captured subtypes with similar patterns of demographic and clinical characteristics, and with similar maps of cortical thinning and tau PET uptake, at the group level. However, large disagreements were found at the individual level.ConclusionsAlthough characteristics of subtypes may be comparable at the group level, there is a large disagreement at the individual level across subtyping methods. Therefore, there is an urgent need for consensus and harmonization across subtyping methods. We call for establishment of an open benchmarking framework to overcome this problem.

Fluoro-pegylated Chalcones as Positron Emission Tomography Probes for in Vivo Imaging of β-Amyloid Plaques in Alzheimer’s Disease

2009 ◽  
Vol 52 (20) ◽  
pp. 6394-6401 ◽  
Author(s):  
Masahiro Ono ◽  
Rumi Watanabe ◽  
Hidekazu Kawashima ◽  
Yan Cheng ◽  
Hiroyuki Kimura ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
In Vivo Imaging ◽  
Amyloid Plaques ◽  
Emission Tomography ◽  
Positron Emission ◽  
Β Amyloid

scholarly journals Identifying Preclinical Alzheimer’s Disease Using Everyday Driving Behavior: Proof of Concept

2020 ◽  
pp. 1-6
Author(s):  
Ganesh M. Babulal ◽  
Ann Johnson ◽  
Anne M. Fagan ◽  
John C. Morris ◽  
Catherine M. Roe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Driving Behavior ◽  
Amyloid Pet ◽  
Preclinical Alzheimer’S Disease ◽  
Neuropsychological Measures ◽  
Receiver Operating Characteristic Curves ◽  
Preclinical Ad ◽  
Positron Emission

We examined whether driving behavior can predict preclinical Alzheimer’s disease (AD). Data from 131 cognitively normal older adults with cerebrospinal fluid (CSF) and/or positron emission tomography (PET) biomarkers were examined with naturalistic driving behavior. Receiver operating characteristic curves were used to predict the highest 10%, 25%, and 50% of values for CSF tau/Aβ42, ptau181/Aβ42, or amyloid PET. Six in vivo driving variables alone yielded area under the curves (AUC) from 0.64–0.82. Addition of age, Apolipoprotein ɛ4, and neuropsychological measures to the models improved the AUC (0.81 to 0.90). Driving can be used as novel neurobehavioral marker to identify presence of preclinical AD.

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