Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease

Brain, Год журнала: 2016, Номер 139(5), С. 1551 - 1567

Опубликована: Март 8, 2016

SEE SARAZIN ET AL DOI101093/BRAIN/AWW041 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The advent of the positron emission tomography tracer (18)F-AV1451 provides unique opportunity to visualize regional distribution tau pathology in living human brain. In this study, we tested hypothesis that is closely linked symptomatology and patterns glucose hypometabolism Alzheimer's disease, contrast more diffuse amyloid-β pathology. We included 20 patients meeting criteria for probable disease dementia or mild cognitive impairment due presenting with a variety clinical phenotypes, 15 amyloid-β-negative cognitively normal individuals, who underwent (tau), (11)C-PiB (amyloid-β) (18)F-FDG (glucose metabolism) tomography, apolipoprotein E (APOE) genotyping neuropsychological testing. Voxel-wise contrasts against controls (at P < 0.05 family-wise error corrected) showed posterior cortical atrophy ('visual variant disease', n = 7) specifically targeted clinically affected brain regions, while bound diffusely throughout neocortex. Patients an amnestic-predominant presentation (n 5) highest retention medial temporal lateral temporoparietal regions. logopenic primary progressive aphasia ('language demonstrated asymmetric left greater than right hemisphere uptake three five patients. Across 30 FreeSurfer-defined regions interest 16 all scans available, there was strong negative association between (Pearson's r -0.49 ± 0.07, 0.001) less pronounced positive associations 0.16 0.09, 0.18 0.001). linear regressions thresholded at (uncorrected) that, across patients, younger age associated wide neocortex, older increased lobe. APOE ϵ4 carriers parietal non-carriers. Finally, worse performance on domain-specific tests key implicated memory (medial lobes), visuospatial function (occipital, cortex) language (left > cortex). conclusion, imaging-contrary imaging-shows anatomical heterogeneity disease. Although preliminary, these results are consistent expand upon findings from post-mortem, animal cerebrospinal fluid studies, suggest pathological aggregation neurodegeneration manifestations

Язык: Английский

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Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease

Nature Medicine, Год журнала: 2019, Номер 25(2), С. 277 - 283

Опубликована: Янв. 21, 2019

Язык: Английский

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OASIS-3: Longitudinal Neuroimaging, Clinical, and Cognitive Dataset for Normal Aging and Alzheimer Disease

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2019, Номер unknown

Опубликована: Дек. 15, 2019

ABSTRACT OASIS-3 is a compilation of MRI and PET imaging related clinical data for 1098 participants who were collected across several ongoing studies in the Washington University Knight Alzheimer Disease Research Center over course 15 years. Participants include 605 cognitively normal adults 493 individuals at various stages cognitive decline ranging age from 42 to 95 The dataset contains 2000 MR sessions, including multiple structural functional sequences. metabolic amyloid includes 1500 raw scans accompanying post-processed files Unified Pipeline (PUP) are also available OASIS-3. such as volumetric segmentations analyses. Imaging accompanied by dementia APOE status longitudinal outcomes. an open access set scientific community answer questions healthy aging dementia.

Язык: Английский

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Automated classification of Alzheimer's disease and mild cognitive impairment using a single MRI and deep neural networks

NeuroImage Clinical, Год журнала: 2018, Номер 21, С. 101645 - 101645

Опубликована: Дек. 18, 2018

We built and validated a deep learning algorithm predicting the individual diagnosis of Alzheimer's disease (AD) mild cognitive impairment who will convert to AD (c-MCI) based on single cross-sectional brain structural MRI scan. Convolutional neural networks (CNNs) were applied 3D T1-weighted images from ADNI subjects recruited at our Institute (407 healthy controls [HC], 418 AD, 280 c-MCI, 533 stable MCI [s-MCI]). CNN performance was tested in distinguishing c-MCI s-MCI. High levels accuracy achieved all classifications, with highest rates vs HC classification tests using both dataset only (99%) combined + non-ADNI (98%). CNNs discriminated s-MCI patients an up 75% no difference between images. provide powerful tool for automatic patient along continuum. Our method performed well without any prior feature engineering regardless variability imaging protocols scanners, demonstrating that it is exploitable by not-trained operators likely be generalizable unseen data. may accelerate adoption routine practice help assessment management patients.

Язык: Английский

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Tau PET imaging in neurodegenerative tauopathies—still a challenge

Molecular Psychiatry, Год журнала: 2019, Номер 24(8), С. 1112 - 1134

Опубликована: Янв. 11, 2019

The accumulation of pathological misfolded tau is a feature common to collective neurodegenerative disorders known as tauopathies, which Alzheimer's disease (AD) the most common. Related tauopathies include progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), Down's (DS), Parkinson's (PD), and dementia with Lewy bodies (DLB). Investigation role pathology in onset progression these now possible due recent advent tau-specific ligands for use positron emission tomography (PET), including first- (e.g., [18F]THK5317, [18F]THK5351, [18F]AV1451, [11C]PBB3) second-generation compounds [namely [18F]MK-6240, [18F]RO-948 (previously referred [18F]RO69558948), [18F]PI-2620, [18F]GTP1, [18F]PM-PBB3, [18F]JNJ64349311 ([18F]JNJ311) its derivative [18F]JNJ-067)]. In this review we describe discuss findings from vitro vivo studies using both initial new ligands, their relation biomarkers amyloid-β neurodegeneration, cognitive findings. Lastly, methodological considerations quantification ligand binding are addressed, along potential future applications PET, therapeutic trials.

Язык: Английский

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Tau imaging: early progress and future directions

The Lancet Neurology, Год журнала: 2014, Номер 14(1), С. 114 - 124

Опубликована: Дек. 8, 2014

Язык: Английский

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Amyloid-β-independent regulators of tau pathology in Alzheimer disease

Nature reviews. Neuroscience, Год журнала: 2019, Номер 21(1), С. 21 - 35

Опубликована: Ноя. 28, 2019

Язык: Английский

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Metabolic network failures in Alzheimer's disease: A biochemical road map

Alzheimer s & Dementia, Год журнала: 2017, Номер 13(9), С. 965 - 984

Опубликована: Март 21, 2017

Abstract Introduction The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, nonprofit organizations to develop new research directions transform our understanding disease (AD) propel the development critically needed therapies. In response their recommendations, big data at multiple levels are being generated integrated study network failures in disease. We used metabolomics as a global biochemical approach identify peripheral metabolic changes AD patients correlate them cerebrospinal fluid pathology markers, imaging features, cognitive performance. Methods Fasting serum samples Neuroimaging Initiative (199 control, 356 mild impairment, 175 participants) were analyzed using AbsoluteIDQ‐p180 kit. Performance was validated blinded replicates, values medication adjusted. Results Multivariable‐adjusted analyses showed that sphingomyelins ether‐containing phosphatidylcholines altered preclinical biomarker‐defined stages, whereas acylcarnitines several amines, including branched‐chain amino acid valine α‐aminoadipic acid, changed symptomatic stages. Several analytes consistent associations Rotterdam, Erasmus Rucphen Family, Indiana Memory Aging Studies. Partial correlation networks constructed for Aβ 1–42 , tau, imaging, provided initial insights disease‐related processes. Coexpression interconnected key effectors Discussion Metabolomics identified disease‐progression‐related changes. Defining during trajectory its relationship clinical phenotypes provides powerful roadmap drug biomarker discovery.

Язык: Английский

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Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

The Lancet Neurology, Год журнала: 2017, Номер 16(7), С. 552 - 563

Опубликована: Июнь 14, 2017

Язык: Английский

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BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease

Alzheimer s Research & Therapy, Год журнала: 2014, Номер 6(9)

Опубликована: Дек. 23, 2014

Abstract β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the β-secretase required for production of neurotoxic β-amyloid (Aβ) peptide that widely considered to have a crucial early role in etiology Alzheimer’s disease (AD). As result, BACE1 has emerged as prime drug target reducing levels Aβ AD brain, and development inhibitors therapeutic agents being vigorously pursued. It proven difficult pharmaceutical industry design inhibitor drugs pass blood–brain barrier, however this challenge recently been met are now human clinical trials test safety efficacy patients individuals with pre-symptomatic AD. Initial results suggest some these well tolerated, although others dropped out because toxicity it still too know whether any will be effective prevention or treatment Additionally, based on newly identified substrates phenotypes mice lack BACE1, concerns about potential mechanism-based side effects chronic administration. hoped window can achieved balances efficacy. This review summarizes current state progress evaluation their

Язык: Английский

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