Blood Cerebrospinal Fluid Barrier Function Disturbance can be Followed by β-amyloid Accumulation Article Swipe
Yuji Suzuki
,
Yukimi Nakamura
,
Hironaka Igarashi
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-880043/v1
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-880043/v1
Background: Elucidation of the mechanism of β-amyloid accumulation plays an important role in therapeutic strategies for Alzheimer’s disease (AD). To elucidate the relationship between the function of the blood cerebrospinal fluid barrier (BCSFB) and the production and clearance of β-amyloid, we analyzed the changes in interstitial water flow into the CSF space from the cortex and β-amyloid accumulation in the cortex by using both [ 15 O]H 2 O and [ 18 F]flutemetamol PET over a 2-year follow-up period. Methods: Twenty-five normal older adult volunteers (13 males and 12 females, 60–81 years old) participated in this 2-year follow-up PET study. Water dynamics were analyzed using two indices in [ 15 O]H 2 O PET, the influx ratio (IR) and drain rate (DR), and β-amyloid accumulation was assessed qualitatively by [ 18 F]flutemetamol PET. Results: [ 15 O]H 2 O PET examinations conducted initially and after 2 years showed no significant changes in both indices over the 2-year period (IR: 1.03 ± 0.21 and 1.02 ± 0.20, DR: 1.74 ± 0.43 and 1.67 ± 0.47, respectively). In [ 18 F]flutemetamol PET, on the other hand, one of the 25 participants showed positive results and two showed positive changes after 2 years. In these three participants, the two indices of water dynamics showed low values at both periods (IR: 0.60 ± 0.15 and 0.60 ± 0.13, DR: 1.24 ± 0.12 and 1.11 ± 0.10). Conclusions: Our results indicated that BCSFB function disturbances could be followed by β-amyloid accumulation, because the reduced interstitial flow preceded amyloid accumulation in the positive-change subjects, and amyloid accumulation was not observed in the older adults with sufficiently high values for the two indices. In other words, adequate interstitial flow can potentially prevent amyloid accumulation. The current study confirms that disturbances in the proper clearance of β-amyloid by interstitial flow through the Virchow–Robin spaces into the CSF can play a significant role in senile plaque formation and ultimately the pathogenesis of AD. We believe that further elucidation of interstitial water flow will be the key to developing therapeutic strategies for AD, especially with regard to prevention.Trial registration: UMIN, UMIN000011939. Registered 1November 2013 - Retrospectively registered, http://www.umin.ac.jp/ctr/index.htm
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-880043/v1
- https://www.researchsquare.com/article/rs-880043/latest.pdf
- OA Status
- green
- References
- 18
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3201560973
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3201560973Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-880043/v1Digital Object Identifier
- Title
-
Blood Cerebrospinal Fluid Barrier Function Disturbance can be Followed by β-amyloid AccumulationWork title
- Type
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preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-09-20Full publication date if available
- Authors
-
Yuji Suzuki, Yukimi Nakamura, Hironaka IgarashiList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-880043/v1Publisher landing page
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https://www.researchsquare.com/article/rs-880043/latest.pdfDirect link to full text PDF
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YesWhether a free full text is available
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-
greenOpen access status per OpenAlex
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https://www.researchsquare.com/article/rs-880043/latest.pdfDirect OA link when available
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Cerebrospinal fluid, Disturbance (geology), Blood–brain barrier, Amyloid (mycology), Function (biology), Medicine, Pathology, Neuroscience, Biology, Cell biology, Central nervous system, PaleontologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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18Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.from | 53 |
| abstract_inverted_index.high | 271 |
| abstract_inverted_index.into | 49, 307 |
| abstract_inverted_index.old) | 93 |
| abstract_inverted_index.over | 75, 155 |
| abstract_inverted_index.play | 311 |
| abstract_inverted_index.rate | 121 |
| abstract_inverted_index.role | 12, 314 |
| abstract_inverted_index.that | 237, 292, 327 |
| abstract_inverted_index.this | 96 |
| abstract_inverted_index.were | 103 |
| abstract_inverted_index.will | 334 |
| abstract_inverted_index.with | 269, 345 |
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| abstract_inverted_index.(DR), | 122 |
| abstract_inverted_index.0.13, | 224 |
| abstract_inverted_index.0.20, | 166 |
| abstract_inverted_index.0.47, | 174 |
| abstract_inverted_index.BCSFB | 238 |
| abstract_inverted_index.UMIN, | 350 |
| abstract_inverted_index.Water | 101 |
| abstract_inverted_index.adult | 84 |
| abstract_inverted_index.after | 145, 198 |
| abstract_inverted_index.blood | 29 |
| abstract_inverted_index.could | 241 |
| abstract_inverted_index.drain | 120 |
| abstract_inverted_index.fluid | 31 |
| abstract_inverted_index.hand, | 184 |
| abstract_inverted_index.males | 87 |
| abstract_inverted_index.older | 83, 267 |
| abstract_inverted_index.other | 183, 278 |
| abstract_inverted_index.plays | 9 |
| abstract_inverted_index.ratio | 117 |
| abstract_inverted_index.space | 52 |
| abstract_inverted_index.study | 290 |
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| abstract_inverted_index.three | 203 |
| abstract_inverted_index.using | 63, 105 |
| abstract_inverted_index.water | 47, 209, 332 |
| abstract_inverted_index.years | 92, 147 |
| abstract_inverted_index.0.10). | 232 |
| abstract_inverted_index.2-year | 77, 97, 157 |
| abstract_inverted_index.adults | 268 |
| abstract_inverted_index.cortex | 55, 61 |
| abstract_inverted_index.influx | 116 |
| abstract_inverted_index.normal | 82 |
| abstract_inverted_index.period | 158 |
| abstract_inverted_index.plaque | 317 |
| abstract_inverted_index.proper | 296 |
| abstract_inverted_index.regard | 346 |
| abstract_inverted_index.senile | 316 |
| abstract_inverted_index.showed | 148, 190, 195, 211 |
| abstract_inverted_index.spaces | 306 |
| abstract_inverted_index.study. | 100 |
| abstract_inverted_index.values | 213, 272 |
| abstract_inverted_index.words, | 279 |
| abstract_inverted_index.years. | 200 |
| abstract_inverted_index.(BCSFB) | 33 |
| abstract_inverted_index.60–81 | 91 |
| abstract_inverted_index.amyloid | 253, 260, 286 |
| abstract_inverted_index.barrier | 32 |
| abstract_inverted_index.because | 247 |
| abstract_inverted_index.believe | 326 |
| abstract_inverted_index.between | 24 |
| abstract_inverted_index.changes | 44, 151, 197 |
| abstract_inverted_index.current | 289 |
| abstract_inverted_index.disease | 18 |
| abstract_inverted_index.further | 328 |
| abstract_inverted_index.indices | 107, 154, 207 |
| abstract_inverted_index.period. | 79 |
| abstract_inverted_index.periods | 216 |
| abstract_inverted_index.prevent | 285 |
| abstract_inverted_index.reduced | 249 |
| abstract_inverted_index.results | 192, 235 |
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| abstract_inverted_index.Results: | 134 |
| abstract_inverted_index.adequate | 280 |
| abstract_inverted_index.analyzed | 42, 104 |
| abstract_inverted_index.assessed | 127 |
| abstract_inverted_index.confirms | 291 |
| abstract_inverted_index.dynamics | 102, 210 |
| abstract_inverted_index.females, | 90 |
| abstract_inverted_index.followed | 243 |
| abstract_inverted_index.function | 26, 239 |
| abstract_inverted_index.indices. | 276 |
| abstract_inverted_index.observed | 264 |
| abstract_inverted_index.positive | 191, 196 |
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| abstract_inverted_index.1November | 353 |
| abstract_inverted_index.clearance | 38, 297 |
| abstract_inverted_index.conducted | 142 |
| abstract_inverted_index.elucidate | 21 |
| abstract_inverted_index.follow-up | 78, 98 |
| abstract_inverted_index.formation | 318 |
| abstract_inverted_index.important | 11 |
| abstract_inverted_index.indicated | 236 |
| abstract_inverted_index.initially | 143 |
| abstract_inverted_index.mechanism | 5 |
| abstract_inverted_index.subjects, | 258 |
| abstract_inverted_index.Registered | 352 |
| abstract_inverted_index.developing | 339 |
| abstract_inverted_index.especially | 344 |
| abstract_inverted_index.production | 36 |
| abstract_inverted_index.strategies | 15, 341 |
| abstract_inverted_index.ultimately | 320 |
| abstract_inverted_index.volunteers | 85 |
| abstract_inverted_index.β-amyloid | 7, 57, 124, 245, 299 |
| abstract_inverted_index.Background: | 1 |
| abstract_inverted_index.Elucidation | 2 |
| abstract_inverted_index.Twenty-five | 81 |
| abstract_inverted_index.elucidation | 329 |
| abstract_inverted_index.potentially | 284 |
| abstract_inverted_index.registered, | 357 |
| abstract_inverted_index.significant | 150, 313 |
| abstract_inverted_index.therapeutic | 14, 340 |
| abstract_inverted_index.β-amyloid, | 40 |
| abstract_inverted_index.Conclusions: | 233 |
| abstract_inverted_index.accumulation | 8, 58, 125, 254, 261 |
| abstract_inverted_index.disturbances | 240, 293 |
| abstract_inverted_index.examinations | 141 |
| abstract_inverted_index.interstitial | 46, 250, 281, 301, 331 |
| abstract_inverted_index.participants | 189 |
| abstract_inverted_index.participated | 94 |
| abstract_inverted_index.pathogenesis | 322 |
| abstract_inverted_index.relationship | 23 |
| abstract_inverted_index.sufficiently | 270 |
| abstract_inverted_index.Alzheimer’s | 17 |
| abstract_inverted_index.accumulation, | 246 |
| abstract_inverted_index.accumulation. | 287 |
| abstract_inverted_index.cerebrospinal | 30 |
| abstract_inverted_index.participants, | 204 |
| abstract_inverted_index.qualitatively | 128 |
| abstract_inverted_index.registration: | 349 |
| abstract_inverted_index.F]flutemetamol | 73, 132, 179 |
| abstract_inverted_index.UMIN000011939. | 351 |
| abstract_inverted_index.respectively). | 175 |
| abstract_inverted_index.Retrospectively | 356 |
| abstract_inverted_index.Virchow–Robin | 305 |
| abstract_inverted_index.positive-change | 257 |
| abstract_inverted_index.prevention.Trial | 348 |
| abstract_inverted_index.http://www.umin.ac.jp/ctr/index.htm | 358 |
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| countries_distinct_count | 1 |
| institutions_distinct_count | 3 |
| corresponding_institution_ids | https://openalex.org/I71395657 |
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| citation_normalized_percentile.is_in_top_10_percent | False |