Abstract:
BACKGROUND:Imaging agents capable of quantifying the brain's tau aggregates will allow a more precise staging of Alzheimer's disease (AD). The aim of the present study was to examine the in vitro properties as well as the in vivo kinetics, using gold standard methods, of the novel positron emission tomography (PET) tau imaging agent [18F]MK-6240. METHODS:In vitro properties of [18F]MK-6240 were estimated with autoradiography in postmortem brain tissues of 14 subjects (seven AD patients and seven age-matched controls). In vivo quantification of [18F]MK-6240 binding was performed in 16 subjects (four AD patients, three mild cognitive impairment patients, six healthy elderly individuals, and three healthy young individuals) who underwent 180-min dynamic scans; six subjects had arterial sampling for metabolite correction. Simplified approaches for [18F]MK-6240 quantification were validated using full kinetic modeling with metabolite-corrected arterial input function. All participants also underwent amyloid-PET and structural magnetic resonance imaging. RESULTS:In vitro [18F]MK-6240 uptake was higher in AD patients than in age-matched controls in brain regions expected to contain tangles such as the hippocampus, whereas no difference was found in the cerebellar gray matter. In vivo, [18F]MK-6240 displayed favorable kinetics with rapid brain delivery and washout. The cerebellar gray matter had low binding across individuals, showing potential for use as a reference region. A reversible two-tissue compartment model well described the time-activity curves across individuals and brain regions. Distribution volume ratios using the plasma input and standardized uptake value ratios (SUVRs) calculated after the binding approached equilibrium (90 min) were correlated and higher in mild cognitive impairment or AD dementia patients than in controls. Reliability analysis revealed robust SUVRs calculated from 90 to 110 min, while earlier time points provided inaccurate estimates. CONCLUSIONS:This evaluation shows an [18F]MK-6240 distribution in concordance with postmortem studies and that simplified quantitative approaches such as the SUVR offer valid estimates of neurofibrillary tangle load 90 min post injection. [18F]MK-6240 is a promising tau tracer with the potential to be applied in the disease diagnosis and assessment of therapeutic interventions.
journal_name
Alzheimers Res Therjournal_title
Alzheimer's research & therapyauthors
Pascoal TA,Shin M,Kang MS,Chamoun M,Chartrand D,Mathotaarachchi S,Bennacef I,Therriault J,Ng KP,Hopewell R,Bouhachi R,Hsiao HH,Benedet AL,Soucy JP,Massarweh G,Gauthier S,Rosa-Neto Pdoi
10.1186/s13195-018-0402-ysubject
Has Abstractpub_date
2018-07-31 00:00:00pages
74issue
1issn
1758-9193pii
10.1186/s13195-018-0402-yjournal_volume
10pub_type
杂志文章abstract:BACKGROUND:Determination of β-amyloid (Aβ) positivity and likelihood of underlying Alzheimer's disease (AD) relies on dichotomous biomarker cut-off values. Individuals with mild cognitive impairment (MCI) and Aβ within the normal range may still have a substantial risk of developing dementia, primarily of Alzheimer typ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0557-1
更新日期:2019-12-05 00:00:00
abstract::Alzheimer's disease (AD) is the most common cause of dementia and a major contributor to disability and dependency among older people. AD pathogenesis is associated with the accumulation of amyloid-beta protein (Aβ) and/or hyperphosphorylated tau protein in the brain. At present, current therapies provide temporary sy...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/alzrt237
更新日期:2014-01-30 00:00:00
abstract:BACKGROUND:In patients with amyloid-positive mild cognitive impairment (MCI), neurodegenerative biomarkers such as medial temporal lobe atrophy (MTA) are useful to predict disease progression to dementia. Although posterior atrophy (PA) is a well-known neurodegenerative biomarker of Alzheimer's disease, little is known...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-017-0326-y
更新日期:2017-12-16 00:00:00
abstract:BACKGROUND:Amyloid-β 1-42 (Aβ1-42) peptide is a well-established cerebrospinal fluid (CSF) biomarker for Alzheimer's disease (AD). Reduced levels of Aβ1-42 are indicative of AD, but significant variation in the absolute concentrations of this analyte has been described for both healthy and diseased populations. Preanal...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0445-0
更新日期:2018-11-28 00:00:00
abstract:BACKGROUND:Association between kidney dysfunction and dementia has been studied in western cohorts, but with inconsistent conclusions which may be due to the different measurements of kidney function. We aim to verify the hypothesis that lower levels of kidney function would be associated with increased risk of inciden...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00729-9
更新日期:2021-01-11 00:00:00
abstract:INTRODUCTION:There have been recent reports about a decline in dementia incidence, but only little is known about trends in the mortality of patients with dementia. Only the simultaneous analysis of both trends can inform whether the reported decline in dementia has led to a compression of dementia into higher ages. M...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-015-0146-x
更新日期:2015-11-05 00:00:00
abstract:BACKGROUND:[18F]FDG-PET hypometabolism patterns are indicative of different neurodegenerative conditions, even from the earliest disease phase. This makes [18F]FDG-PET a valuable tool in the diagnostic workup of neurodegenerative diseases. The utility of [18F]FDG-PET in dementia with Lewy bodies (DLB) needs further val...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0473-4
更新日期:2019-02-23 00:00:00
abstract:INTRODUCTION:Depression and psychosis are two of the most severe neuropsychiatric symptoms (NPS) in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Both NPS have negative effects on cognitive performance and life expectancy. The current study aimed to investigate and compare monoaminergic etiologies betwe...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-014-0090-1
更新日期:2015-02-11 00:00:00
abstract:BACKGROUND:Down syndrome (DS), caused by chromosome 21 trisomy, is associated with an ultra-high risk of dementia due to Alzheimer's disease (AD), driven by amyloid precursor protein (APP) gene triplication. Understanding relevant molecular differences between those with DS, those with sporadic AD (sAD) without DS, and...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0477-0
更新日期:2019-03-21 00:00:00
abstract:BACKGROUND:Mild cognitive impairment (MCI) has an uncertain etiology and prognosis and may be challenging for clinicians to discuss with patients and families. Amyloid imaging may aid specialists in determining MCI etiology and prognosis, but creates novel challenges related to disease labeling. METHODS:We convened a ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-017-0261-y
更新日期:2017-05-04 00:00:00
abstract:BACKGROUND:Animal models of Alzheimer's disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing th...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0346-2
更新日期:2018-02-07 00:00:00
abstract::In May 2012, the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia brought together in Montreal experts from around Canada to update Canadian recommendations for the diagnosis and management of patients with neurodegenerative conditions associated with deterioration of cognition. Multiple...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt199
更新日期:2013-07-08 00:00:00
abstract:BACKGROUND:Our objectives were to develop a disease progression model for cognitive decline in Alzheimer's disease (AD) and to determine whether disease progression of AD is related to the year of publication, add-on trial design, and geographical regions. METHODS:Placebo-controlled randomized AD clinical trials were ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00630-5
更新日期:2020-05-26 00:00:00
abstract::Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is mo...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/alzrt239
更新日期:2014-02-24 00:00:00
abstract:BACKGROUND:The Centiloid scale has been developed to standardize measurements of amyloid PET imaging. Reference cut-off values of this continuous measurement enable the consistent operationalization of decision-making for multicentre research studies and clinical trials. In this study, we aimed at deriving reference Ce...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0478-z
更新日期:2019-03-21 00:00:00
abstract:BACKGROUND:In Alzheimer's disease, beta-amyloid peptides in the brain aggregate into toxic oligomers and plaques, a process which is associated with neuronal degeneration, memory loss, and cognitive decline. One therapeutic strategy is to decrease the production of potentially toxic beta-amyloid species by the use of i...
journal_title:Alzheimer's research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/s13195-016-0178-x
更新日期:2016-03-07 00:00:00
abstract:INTRODUCTION:There has been a significant increase in the use of testosterone in aging men, but little investigation into its impact on men with Alzheimer's disease (AD). The findings of the few studies that have been done are inconsistent. In the present study, we investigated the relationship between total testostero...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-015-0107-4
更新日期:2015-05-01 00:00:00
abstract:BACKGROUND:Several monoclonal antibodies for the treatment of Alzheimer's disease (AD) have been in development over the last decade. BAN2401 is a monoclonal antibody that selectively binds soluble amyloid β (Aβ) protofibrils. METHODS:Here we describe the first clinical study with BAN2401. Safety and tolerability were...
journal_title:Alzheimer's research & therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1186/s13195-016-0181-2
更新日期:2016-04-06 00:00:00
abstract:BACKGROUND:Dementia has been presenting an imminent public health challenge worldwide. Studies have shown a combination of cognitive and physical trainings may have synergistic value for improving cognitive functions. Daily functional tasks are innately cognitive demanding and involve components found in common exercis...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13195-019-0548-2
更新日期:2019-12-04 00:00:00
abstract:BACKGROUND:Given the growing older population worldwide, and the associated increase in age-related diseases, such as Alzheimer's disease (AD), investigating non-invasive methods to ameliorate or even prevent cognitive decline in prodromal AD is highly relevant. Previous studies suggest transcranial direct current stim...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00692-5
更新日期:2020-11-07 00:00:00
abstract:INTRODUCTION:Behavioural and psychological symptoms of dementia (BPS) include depressive symptoms, anxiety, apathy, sleep problems, irritability, psychosis, wandering, elation and agitation, and are common in the non-demented and demented population. METHODS:We have undertaken a systematic review of reviews to give a ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt131
更新日期:2012-07-11 00:00:00
abstract::Recent trials of statins produced no benefit for subjects with Alzheimer's disease. These negative studies add to a growing list of negative clinical trials. These data point to a need for reevaluating the pathophysiology of late-onset Alzheimer's disease. Late-onset Alzheimer's disease might result from the cumulativ...
journal_title:Alzheimer's research & therapy
pub_type: 社论
doi:10.1186/alzrt101
更新日期:2012-01-16 00:00:00
abstract:BACKGROUND:Cerebrovascular pathology, quantified by white matter lesions (WML), is known to affect cognition in aging, and is associated with an increased risk of dementia. The present study aimed to investigate whether higher functional connectivity in cognitive control networks mitigates the detrimental effect of WML...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0434-3
更新日期:2018-10-27 00:00:00
abstract::The oligomer cascade hypothesis, which states that oligomers are the initiating pathologic agents in Alzheimer's disease, has all but supplanted the amyloid cascade hypothesis, which suggested that fibers were the key etiologic agents in Alzheimer's disease. We review here the results of in vivo, in vitro and in silic...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/alzrt226
更新日期:2013-11-29 00:00:00
abstract::The Alzheimer's Drug Discovery Foundation's 13th International Conference on Alzheimer's Drug Discovery was held on 10-11 September 2012 in Jersey City, NJ, USA. This meeting report provides an overview of Alzheimer's Drug Discovery Foundation-funded programs, ranging from novel biomarkers to accelerate clinical devel...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt159
更新日期:2013-02-04 00:00:00
abstract:BACKGROUND:Accumulating evidence implicates the neuroendocrine immunomodulation (NIM) network in the physiopathological mechanism of Alzheimer's disease (AD). Notably, we previously revealed that the NIM network is dysregulated in the PrP-hAβPPswe/PS1ΔE9 (APP/PS1) transgenic mouse model of AD. METHODS:After treatment ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-016-0226-6
更新日期:2016-12-13 00:00:00
abstract:BACKGROUND:Targeting the expression of genes has emerged as a potentially viable therapeutic approach to human disease. In Alzheimer's disease, therapies that silence the expression of tau could be a viable strategy to slow disease progression. METHODS:We produced a novel strain of transgenic mice that could be used t...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-016-0202-1
更新日期:2016-09-05 00:00:00
abstract:INTRODUCTION:Peripheral biomarkers to diagnose Alzheimer's disease (AD) have not been established. Given parallels between neuron and platelet biology, we hypothesized platelet membrane-associated protein changes may differentiate patients clinically defined with probable AD from noncognitive impaired controls. METHOD...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt186
更新日期:2013-06-13 00:00:00
abstract:BACKGROUND:Neuroinflammation has gained increasing attention as a potential contributing factor in Alzheimer's disease (AD) pathology. A clinical cerebrospinal fluid biomarker capable of monitoring this process during the course of the disease has yet to emerge, chiefly owing to contradictory research findings. In this...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0353-3
更新日期:2018-02-26 00:00:00
abstract::The long-term consequences of repetitive head impacts have been described since the early 20th century. Terms such as punch drunk and dementia pugilistica were first used to describe the clinical syndromes experienced by boxers. A more generic designation, chronic traumatic encephalopathy (CTE), has been employed sinc...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-014-0068-z
更新日期:2014-09-24 00:00:00