HTML Microdata document

This HTML5 document contains 322 embedded RDF statements represented using HTML+Microdata notation.

The embedded RDF content will be recognized by any processor of HTML5 Microdata.

Namespace Prefixes

Prefix	IRI
dc	http://purl.org/dc/elements/1.1/
n11	http://pubannotation.org/docs/sourcedb/PMC/sourceid/
n3	http://purl.jp/bio/10/colil/id/
rdfs	http://www.w3.org/2000/01/rdf-schema#
bibo	http://purl.org/ontology/bibo/
n2	http://purl.jp/bio/10/colil/ontology/201303#
rdf	http://www.w3.org/1999/02/22-rdf-syntax-ns#
n8	http://togows.dbcls.jp/entry/pubmed/
n7	http://www.ncbi.nlm.nih.gov/pmc/articles/
n10	http://dx.doi.org/
xsdh	http://www.w3.org/2001/XMLSchema#
n5	http://purl.org/spar/doco/

Statements

Subject Item: n3:33536430
rdf:type: n2:RelevantPaper n2:ReferencePaper n2:CitationPaper
rdfs:seeAlso: n7:0 n8:33536430 n10:10.1038%2Fs41467-021-21022-9 n11:0
bibo:cites: n3:18219254 n3:6733518 n3:22872307 n3:19664710 n3:29222591 n3:30610216 n3:21661055 n3:30602773 n3:21720849 n3:6263475 n3:28039094 n3:11844739 n3:25676160 n3:30953664 n3:28379300 n3:30264465 n3:26891768 n3:25222068 n3:20485502 n3:19039041 n3:31136023 n3:22230573 n3:21596773 n3:24951642 n3:5046750 n3:30123935 n3:28605056 n3:19838705 n3:29317637
n2:cocitationWith: n3:31558719 n3:32284421 n3:27510760 n3:31601988 n3:30792657 n3:27188790 n3:28690161 n3:30214628 n3:21376455 n3:29443965 n3:27420647 n3:30264465 n3:30890548 n3:25270115 n3:30046032 n3:33399511 n3:28511006 n3:28379300 n3:27994152 n3:30280653 n3:28425493 n3:31668690 n3:11526261 n3:30808897 n3:27235980 n3:28045902 n3:26590417 n3:32112904
n2:hasRelevantBibliographicResourceOf: _:vb681334712 _:vb681334713 _:vb681334714 _:vb681334715 _:vb681334716 _:vb681334717 _:vb681334718 _:vb681334719 _:vb681334706 _:vb681334707 _:vb681334708 _:vb681334709 _:vb681334710 _:vb681334711 _:vb681334728 _:vb681334729 _:vb681334730 _:vb681334731 _:vb681334732 _:vb681334733 _:vb681334720 _:vb681334721 _:vb681334722 _:vb681334723 _:vb681334724 _:vb681334725 _:vb681334726 _:vb681334727
n2:pmcid: PMC0
bibo:doi: 10.1038%2Fs41467-021-21022-9
n5:contains: _:vb131962202 _:vb131962219 _:vb131962223 _:vb131962227

Subject Item: _:vb131962202
rdf:type: n5:Section
dc:title: introduction
n5:contains: _:vb131962204 _:vb131962205 _:vb131962206 _:vb131962207 _:vb131962203 _:vb131962216 _:vb131962217 _:vb131962218 _:vb131962212 _:vb131962213 _:vb131962214 _:vb131962215 _:vb131962208 _:vb131962209 _:vb131962210 _:vb131962211

Subject Item: _:vb131962203
rdf:type: n2:Context
rdf:value: The risk of dementia in Parkinson’s disease (PD) is 6–8 times higher than in age-matched controls, and its prevalence reaches 80% in the long-term>>1<<. The essential neurobiological basis for PD is degeneration of nigrostriatal dopamine neurons and pathological deposition of the α-synuclein protein in intraneuronal Lewy inclusions within vulnerable neuronal populations.
n2:mentions: n3:25676160

Subject Item: _:vb131962204
rdf:type: n2:Context
rdf:value: Lewy pathology is generally considered to be an important etiopathogenic factor in the development of cognitive impairment in PD>>2<<. However, the combination of Lewy pathology and Alzheimer’s disease (AD) pathology (amyloid-β plaques and neurofibrillary tangles) is the most robust pathological correlate of dementia in PD (PDD)3. Indeed, the parieto-occipito-temporal
n2:mentions: n3:11844739

Subject Item: _:vb131962205
rdf:type: n2:Context
rdf:value: However, the combination of Lewy pathology and Alzheimer’s disease (AD) pathology (amyloid-β plaques and neurofibrillary tangles) is the most robust pathological correlate of dementia in PD (PDD)>>3<<. Indeed, the parieto-occipito-temporal junction is a prominent site of cortical pathology in PDD, which correlates significantly with cognitive impairment2,4. Numerous clinical trials are currently testing antibodies that target
n2:mentions: n3:21596773

Subject Item: _:vb131962206
rdf:type: n2:Context
rdf:value: Indeed, the parieto-occipito-temporal junction is a prominent site of cortical pathology in PDD, which correlates significantly with cognitive impairment>>2<<,4. Numerous clinical trials are currently testing antibodies that target α-synuclein, tau, and amyloid for AD, PD, progressive supranuclear palsy, and other neurodegenerative diseases, but there have been no striking successes so far5,6.
n2:mentions: n3:11844739

Subject Item: _:vb131962207
rdf:type: n2:Context
rdf:value: Indeed, the parieto-occipito-temporal junction is a prominent site of cortical pathology in PDD, which correlates significantly with cognitive impairment2,>>4<<. Numerous clinical trials are currently testing antibodies that target α-synuclein, tau, and amyloid for AD, PD, progressive supranuclear palsy, and other neurodegenerative diseases, but there have been no striking successes so far5,6.
n2:mentions: n3:24951642

Subject Item: _:vb131962208
rdf:type: n2:Context
rdf:value: Numerous clinical trials are currently testing antibodies that target α-synuclein, tau, and amyloid for AD, PD, progressive supranuclear palsy, and other neurodegenerative diseases, but there have been no striking successes so far>>5<<,6. The blood–brain barrier (BBB) is known to effectively prevent a large number of putative therapeutic molecules from gaining access to the brain.
n2:mentions: n3:30610216

Subject Item: _:vb131962209
rdf:type: n2:Context
rdf:value: Previous approaches to enhance BBB permeability showed low specificity and had safety issues>>7<<. However, MRgFUS in combination with intravenously injected microbubbles can temporarily open the BBB at specific brain targets8. This could allow delivery of drugs directly to the brain, paving the way for disease-modifying therapies9.
n2:mentions: n3:19664710

Subject Item: _:vb131962210
rdf:type: n2:Context
rdf:value: However, MRgFUS in combination with intravenously injected microbubbles can temporarily open the BBB at specific brain targets>>8<<. This could allow delivery of drugs directly to the brain, paving the way for disease-modifying therapies9. FUS-BBB opening per se has resulted in significant reductions in brain pathology and memory improvement in the amyloid AD
n2:mentions: n3:26891768

Subject Item: _:vb131962211
rdf:type: n2:Context
rdf:value: This could allow delivery of drugs directly to the brain, paving the way for disease-modifying therapies>>9<<. FUS-BBB opening per se has resulted in significant reductions in brain pathology and memory improvement in the amyloid AD transgenic mouse model10,11 as well as after delivery of antibodies against beta-amyloid12, and tau13. FUS-BBB
n2:mentions: n3:31136023

Subject Item: _:vb131962212
rdf:type: n2:Context
rdf:value: FUS-BBB opening per se has resulted in significant reductions in brain pathology and memory improvement in the amyloid AD transgenic mouse model>>10<<,11 as well as after delivery of antibodies against beta-amyloid12, and tau13.
n2:mentions: n3:25222068

Subject Item: _:vb131962213
rdf:type: n2:Context
rdf:value: FUS-BBB opening per se has resulted in significant reductions in brain pathology and memory improvement in the amyloid AD transgenic mouse model10,11 as well as after delivery of antibodies against beta-amyloid>>12<<, and tau13.
n2:mentions: n3:20485502

Subject Item: _:vb131962214
rdf:type: n2:Context
rdf:value: FUS-BBB opening per se has resulted in significant reductions in brain pathology and memory improvement in the amyloid AD transgenic mouse model10,11 as well as after delivery of antibodies against beta-amyloid12, and tau>>13<<. FUS-BBB opening has also been used in transgenic mice PD and the MPTP-1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine mouse model to deliver viral vectors that target α-synuclein14 and to enhance neurotrophic protein delivery15.
n2:mentions: n3:28379300

Subject Item: _:vb131962215
rdf:type: n2:Context
rdf:value: FUS-BBB opening has also been used in transgenic mice PD and the MPTP-1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine mouse model to deliver viral vectors that target α-synuclein>>14<< and to enhance neurotrophic protein delivery15.
n2:mentions: n3:30264465

Subject Item: _:vb131962216
rdf:type: n2:Context
rdf:value: FUS-BBB opening has also been used in transgenic mice PD and the MPTP-1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine mouse model to deliver viral vectors that target α-synuclein14 and to enhance neurotrophic protein delivery>>15<<.
n2:mentions: n3:30953664

Subject Item: _:vb131962217
rdf:type: n2:Context
rdf:value: Recently, two phase I clinical trials demonstrated that FUS-BBB opening was safe, feasible, and could be repeated twice in AD patients>>16<< and patients with amyotrophic lateral sclerosis (ALS)17. Here, we report the first study aimed at evaluating the safety, feasibility, and reversibility of FUS-BBB opening in PDD.
n2:mentions: n3:29317637

Subject Item: _:vb131962218
rdf:type: n2:Context
rdf:value: Recently, two phase I clinical trials demonstrated that FUS-BBB opening was safe, feasible, and could be repeated twice in AD patients16 and patients with amyotrophic lateral sclerosis (ALS)>>17<<. Here, we report the first study aimed at evaluating the safety, feasibility, and reversibility of FUS-BBB opening in PDD.
n2:mentions: n3:30602773

Subject Item: _:vb131962219
rdf:type: n5:Section
dc:title: results
n5:contains: _:vb131962220 _:vb131962221 _:vb131962222

Subject Item: _:vb131962220
rdf:type: n2:Context
rdf:value: This is above the suggested threshold for pathological Aβ load (SUVr > 0.50)>>18<< (Supplementary Tables 3 and 4).
n2:mentions: n3:30123935

Subject Item: _:vb131962221
rdf:type: n2:Context
rdf:value: [18F]-FDG PET was consistent with the previously reported hypometabolism found in the posterior cortex, including the right parieto-occipito-temporal cortex, when PDD patients were compared with healthy control subjects>>4<<,19.
n2:mentions: n3:24951642

Subject Item: _:vb131962222
rdf:type: n2:Context
rdf:value: [18F]-FDG PET was consistent with the previously reported hypometabolism found in the posterior cortex, including the right parieto-occipito-temporal cortex, when PDD patients were compared with healthy control subjects4,>>19<<.
n2:mentions: n3:22872307

Subject Item: _:vb131962223
rdf:type: n5:Section
dc:title: methods
n5:contains: _:vb131962224 _:vb131962225 _:vb131962226

Subject Item: _:vb131962224
rdf:type: n2:Context
rdf:value: Details of the procedure>>16<< are summarized below. At each new target, power ramp sonications were performed during the microbubble injection in order to detect the lowest threshold for acoustic activity indication of putative cavitation24.
n2:mentions: n3:29317637

Subject Item: _:vb131962225
rdf:type: n2:Context
rdf:value: Brain [18F]-fluorodeoxyglucose PET imaging was performed in accordance with European Association of Nuclear Medicine procedure guidelines>>31<<. Subjects rested in a quiet, dimly-lit room for 15 min before radiotracer administration and during the uptake period. PET acquisition started 40 min after the intravenous injection of 5 MBq per kg of 18F-labeled fluorodeoxyglucose. On a
n2:mentions: n3:19838705

Subject Item: _:vb131962226
rdf:type: n2:Context
rdf:value: Voxels in the pons were defined based on a normalized mask available in the PETPVE12 toolbox>>32<<. PET emission data were reconstructed with an ordered subset-expectation maximization algorithm, smoothed with a 3D isotropic Gaussian of 2 mm at FWHM, and corrected for attenuation using MR-based maps derived from a dual-echo Dixon-based
n2:mentions: n3:28039094

Subject Item: _:vb131962227
rdf:type: n5:Section
dc:title: discussion
n5:contains: _:vb131962232 _:vb131962233 _:vb131962234 _:vb131962235 _:vb131962236 _:vb131962237 _:vb131962228 _:vb131962229 _:vb131962230 _:vb131962231

Subject Item: _:vb131962228
rdf:type: n2:Context
rdf:value: Some of these strategies include direct intrathecal/intraventricular drug delivery or osmotic opening with hypertonic solutions>>20<<–22, and also modifying the structure of the molecule23.
n2:mentions: n3:6733518 n3:6263475 n3:5046750

Subject Item: _:vb131962229
rdf:type: n2:Context
rdf:value: Some of these strategies include direct intrathecal/intraventricular drug delivery or osmotic opening with hypertonic solutions20–22, and also modifying the structure of the molecule>>23<<. However, all these methods are limited by a lack of topographic specificity, and by safety concerns. FUS coupled with the injection of microbubbles is minimally invasive, transient, and targets specific areas allowing delivery of
n2:mentions: n3:22230573

Subject Item: _:vb131962230
rdf:type: n2:Context
rdf:value: Previous clinical studies of BBB opening in AD and ALS have not included SWAN as part of the study protocol>>16<<,17,24 but did report transient T2* hypointensities in two patients16.
n2:mentions: n3:29317637

Subject Item: _:vb131962231
rdf:type: n2:Context
rdf:value: Previous clinical studies of BBB opening in AD and ALS have not included SWAN as part of the study protocol16,>>17<<,24 but did report transient T2* hypointensities in two patients16.
n2:mentions: n3:30602773

Subject Item: _:vb131962232
rdf:type: n2:Context
rdf:value: Previous clinical studies of BBB opening in AD and ALS have not included SWAN as part of the study protocol16,17,24 but did report transient T2* hypointensities in two patients>>16<<. SWAN signal changes were found in patients # 2, 3, and 4. Patient #1 had no T2* hypointensity but the SWAN image was not available for this patient, so we cannot rule out the possibility of SWAN signal changes. Among patients # 2, 3, and
n2:mentions: n3:29317637

Subject Item: _:vb131962233
rdf:type: n2:Context
rdf:value: T2* sequences>>25<<. Whereas positive SWAN findings have not been associated with any clinical manifestation, these may represent blood extravasation and pathology assessment would be needed to demonstrate histological indemnity.
n2:mentions: n3:19039041

Subject Item: _:vb131962234
rdf:type: n2:Context
rdf:value: PD-MCI is a well-defined entity in PD where the patient has cognitive deficits that do not interfere significantly with functional independence (unlike dementia)>>26<< and it is considered one of the most important risk factors for PDD27.
n2:mentions: n3:21661055

Subject Item: _:vb131962235
rdf:type: n2:Context
rdf:value: PD-MCI is a well-defined entity in PD where the patient has cognitive deficits that do not interfere significantly with functional independence (unlike dementia)26 and it is considered one of the most important risk factors for PDD>>27<<. Therefore, this predementia stage could benefit from specific treatments aiming to prevent progression towards disability and severe cognitive decline.
n2:mentions: n3:28605056

Subject Item: _:vb131962236
rdf:type: n2:Context
rdf:value: Focused BBB opening in PD could be used to target regions predominantly affected pathologically and associated with dementia, such as the striatum, the amygdala, and the parieto-occipito-temporal cortex>>4<<,28–30 but also could target the motor (dorso-lateral) striatum and ventro-lateral substantia nigra pars compacta which sustain the cardinal motor manifestations.
n2:mentions: n3:24951642

Subject Item: _:vb131962237
rdf:type: n2:Context
rdf:value: Focused BBB opening in PD could be used to target regions predominantly affected pathologically and associated with dementia, such as the striatum, the amygdala, and the parieto-occipito-temporal cortex4,>>28<<–30 but also could target the motor (dorso-lateral) striatum and ventro-lateral substantia nigra pars compacta which sustain the cardinal motor manifestations.
n2:mentions: n3:18219254 n3:21720849 n3:29222591

Subject Item: _:vb681334706
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 5
n2:hasRelevantPaperId: n3:30046032

Subject Item: _:vb681334707
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 3
n2:hasRelevantPaperId: n3:31558719

Subject Item: _:vb681334708
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 3
n2:hasRelevantPaperId: n3:30264465

Subject Item: _:vb681334709
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 3
n2:hasRelevantPaperId: n3:32284421

Subject Item: _:vb681334710
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 3
n2:hasRelevantPaperId: n3:31601988

Subject Item: _:vb681334711
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 3
n2:hasRelevantPaperId: n3:27420647

Subject Item: _:vb681334712
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 3
n2:hasRelevantPaperId: n3:11526261

Subject Item: _:vb681334713
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:28511006

Subject Item: _:vb681334714
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:30890548

Subject Item: _:vb681334715
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:27510760

Subject Item: _:vb681334716
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:30808897

Subject Item: _:vb681334717
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:29443965

Subject Item: _:vb681334718
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:31668690

Subject Item: _:vb681334719
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:28045902

Subject Item: _:vb681334720
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:28425493

Subject Item: _:vb681334721
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:32112904

Subject Item: _:vb681334722
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:30280653

Subject Item: _:vb681334723
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:26590417

Subject Item: _:vb681334724
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:27188790

Subject Item: _:vb681334725
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:21376455

Subject Item: _:vb681334726
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:30792657

Subject Item: _:vb681334727
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:30214628

Subject Item: _:vb681334728
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:33399511

Subject Item: _:vb681334729
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:28379300

Subject Item: _:vb681334730
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:27235980

Subject Item: _:vb681334731
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:27994152

Subject Item: _:vb681334732
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:25270115

Subject Item: _:vb681334733
rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 2
n2:hasRelevantPaperId: n3:28690161