Background
Late-onset Alzheimer’s disease (AD) is characterized by primary memory impairment, which then progresses towards severe deficits across cognitive domains. Here, we report how performance in cognitive domains relates to patterns of tau deposition and cortical thickness.
OBJECTIVE: To examine the cross-sectional associations between regional tau, β-amyloid (Aβ), and cortical thickness and neuropsychological function across the preclinical and clinical spectrum of Alzheimer disease (AD). METHODS: We included 106 participants from the Swedish Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study, of whom 33 had preclinical AD (Aβ-positive cognitively normal individuals), 25 had prodromal AD (Aβ-positive mild cognitive impairme...
BACKGROUND: Biomarkers may soon be used to predict decline in older individuals. Extended follow-up studies are needed to determine the stability of such biomarker-based predictions. OBJECTIVE: To examine the long-term performance of baseline cognitive, neuroimaging, and cerebrospinal fluid (CSF) biomarker-assisted prognosis in patients with mild cognitive impairment. METHODS: Established, biomarker-defined, cohorts of subjects with mild cognitive impairment were examined for progression to deme...
Abstract In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a "research framework" because its intended use is for observational and interventional resear...
#2Shubhajit Das(UPenn: University of Pennsylvania)H-Index: 48
Last. Murray Grossman(UPenn: University of Pennsylvania)H-Index: 113
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Accumulation of paired helical filament tau contributes to neurodegeneration in Alzheimer's disease (AD). 18 F-flortaucipir is a positron emission tomography (PET) radioligand sensitive to tau in AD, but its clinical utility will depend in part on its ability to predict cognitive symptoms in diverse dementia phenotypes associated with selective, regional uptake. We examined associations between 18 F-flortaucipir and cognition in 14 mildly-impaired patients (12 with cerebrospinal fluid analytes c...
BACKGROUND: Lilly/Avid's AV-1451 is one of the most advanced tau PET tracers in the clinic. Although results obtained in Alzheimer's disease patients are compelling, discrimination of tracer uptake in healthy individuals and patients with supranuclear palsy (PSP) is less clear as there is substantial overlap of signal in multiple brain regions. Moreover, accurate quantification of [18 F]AV-1451 uptake in Alzheimer's disease may not be possible. OBJECTIVES: The aim of the present study was to cha...
IMPORTANCE Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials. OBJECTIVE To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study included 290...
#1Suzanne L. Baker(LBNL: Lawrence Berkeley National Laboratory)H-Index: 39
#2Anne Maass(HWNI: Helen Wills Neuroscience Institute)H-Index: 23
Last. William J. Jagust(HWNI: Helen Wills Neuroscience Institute)H-Index: 140
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Abstract [ 18 F]-AV-1451 is a leading tracer used with positron emission tomography (PET) to quantify tau pathology. However, [ 18 F]-AV-1451 shows “off target” or non-specific binding, which we define as binding of the tracer in unexpected areas unlikely to harbor aggregated tau based on autopsy literature [1] . Along with caudate, putamen, pallidum and thalamus non-specific binding [2] , [3] , we have found binding in the superior portion of the cerebellar gray matter, leading us to use inferi...
[F-18]-AV-1451 is a novel positron emission tomography (PET) tracer with high affinity to neurofibrillary tau pathology in Alzheimer’s disease (AD). PET studies have shown increased tracer retention in patients clinically diagnosed with dementia of AD type and mild cognitive impairment in regions that are known to contain tau lesions. In vivo uptake has also consistently been observed in midbrain, basal ganglia and choroid plexus in elderly individuals regardless of their clinical diagnosis, inc...
Tauopathies are a heterogeneous class of neurodegenerative diseases characterized by intracellular inclusions of aggregated tau proteins. Tau aggregates in different tauopathies have distinct structural features and can be found in different cell types. Transgenic animal models overexpressing human tau have been used for over two decades in the research of tau pathology. However, these models poorly recapitulate the heterogeneity of tauopathies found in human brains. Recent findings demonstrate ...
BACKGROUND The National Institute on Aging (NIA)/Alzheimer's Association (AA) 2018 framework conceptualizes Alzheimer's disease (AD) biologically. Evidence of brain amyloid by biomarkers defines AD pathologic change and the Alzheimer's continuum. The presence of tau or neurodegeneration in the absence of amyloid defines non-AD pathologic change. OBJECTIVE To examine the relation of in vivo amyloid and neurodegeneration with verbal learning, one of the cognitive abilities affected early in AD, in...
Pathological accumulated misfolded tau underlies various neurodegenerative diseases and associated clinical syndromes. To diagnose those diseases reliable before death or even at early stages, many different tau-specific radiotracers have been developed in the last decade to be used with positron-emission-tomography. In contrast to amyloid-β imaging, different isoforms of tau exist further complicating radiotracer development. First-generation radiotracers like [11C]PBB3, [18F]AV1451 and [18F]TH...
Tauvid has been approved by the U.S. Food and Drug Administration (FDA) in 2020 for positron emission tomography (PET) imaging of adult patients with cognitive impairments undergoing evaluation for Alzheimer’s disease (AD) based on tau pathology. Abnormal aggregation of tau proteins is one of the main pathologies present in AD and is receiving increasing attention as a diagnostic and therapeutic target. In this review, we summarised the production and quality control of Tauvid, its clinical appl...
#1Xi Chen(LBNL: Lawrence Berkeley National Laboratory)H-Index: 11
#2Kaitlin Cassady(HWNI: Helen Wills Neuroscience Institute)H-Index: 9
Last. William J. Jagust(HWNI: Helen Wills Neuroscience Institute)H-Index: 140
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Studies suggest that tau deposition starts in the anterolateral entorhinal cortex (EC) with normal aging, and that the presence of β-amyloid (Aβ) facilitates its spread to neocortex, which may reflect the beginning of Alzheimer's disease (AD). Functional connectivity between the anterolateral EC and the anterior-temporal (AT) memory network appears to drive higher tau deposition in AT than in the posterior-medial (PM) memory network. Here, we investigated whether this differential vulnerability ...
A deeper understanding of the spatial relationships of β-amyloid (Aβ), tau, and neurodegeneration in Alzheimer's disease (AD) could provide insight into pathogenesis and clinical trial design. We included 81 amyloid-positive patients (age 64.4 ± 9.5) diagnosed with AD dementia or mild cognitive impairment due to AD and available 11C-PiB (PIB), 18F-Flortaucipir (FTP),18F-FDG-PET, and 3T-MRI, and 31 amyloid-positive, cognitively normal participants (age 77.3 ± 6.5, no FDG-PET). W-score voxel-wise ...
#1Nicolai Franzmeier(LMU: Ludwig Maximilian University of Munich)H-Index: 18
#2Anna Dewenter(LMU: Ludwig Maximilian University of Munich)H-Index: 1
Last. Michael Ewers(LMU: Ludwig Maximilian University of Munich)H-Index: 56
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In Alzheimer's disease (AD), the Braak staging scheme suggests a stereotypical tau spreading pattern that does, however, not capture interindividual variability in tau deposition. This complicates the prediction of tau spreading, which may become critical for defining individualized tau-PET readouts in clinical trials. Since tau is assumed to spread throughout connected regions, we used functional connectivity to improve tau spreading predictions over Braak staging methods. We included two sampl...
PURPOSE We aimed to investigate associations between tau pathology and relative cerebral blood flow (rCBF), and their relationship with cognition in Alzheimer's disease (AD), by using a single dynamic [18F]flortaucipir positron emission tomography (PET) scan. METHODS Seventy-one subjects with AD (66 ± 8 years, mini-mental state examination (MMSE) 23 ± 4) underwent a dynamic 130-min [18F]flortaucipir PET scan. Cognitive assessment consisted of composite scores of four cognitive domains. For tau p...
#1Tian Tu(CSU: Central South University)H-Index: 2
#2Juan Jiang(CSU: Central South University)H-Index: 3
Last. Xiao-Xin Yan(CSU: Central South University)H-Index: 31
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Amyloid plaques and neurofibrillary tangles (NFT) are hallmark lesions of Alzheimer’s disease (AD) related to β-amyloid (Aβ) deposition and intraneuronal phosphorylated-tau (pTau) accumulation. Sortilin C-terminal fragments (shortened as “sorfra”) can deposit as senile plaque-like lesions within AD brains. The course and pattern of sorfra plaque formation relative to Aβ and pTau pathogenesis remains unknown. In the present study cerebral and subcortical brain regions in postmortem human brains (...
: While amyloid-targeting therapies continue to predominate in the Alzheimer's disease (AD) drug development pipeline, there is increasing recognition that to effectively treat the disease it may be necessary to target other mechanisms and pathways as well. In December 2019, The EU/US CTAD Task Force discussed these alternative approaches to disease modification in AD, focusing on tau-targeting therapies, neurotrophin receptor modulation, anti-microbial strategies, and the innate immune response...