Brain areas with normatively greater cerebral perfusion in early life may be more susceptible to beta amyloid deposition in late life
Background: The amyloid cascade hypothesis characterizes the stereotyped progression of pathological changes in Alzheimer's disease (AD) beginning with beta amyloid deposition, but does not address the reasons for amyloid deposition. Brain areas with relatively higher neuronal activity, metabol...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Cerebral Circulation - Cognition and Behavior |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666245020300015 |
| _version_ | 1797965311651086336 |
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| author | Irene B. Meier Patrick J. Lao Anton Gietl Robert S. Vorburger José Gutierrez Christopher M. Holland Charles R.G. Guttmann Dominik S. Meier Alfred Buck Roger M. Nitsch Christoph Hock Paul G. Unschuld Adam M. Brickman |
| author_facet | Irene B. Meier Patrick J. Lao Anton Gietl Robert S. Vorburger José Gutierrez Christopher M. Holland Charles R.G. Guttmann Dominik S. Meier Alfred Buck Roger M. Nitsch Christoph Hock Paul G. Unschuld Adam M. Brickman |
| author_sort | Irene B. Meier |
| collection | DOAJ |
| description | Background: The amyloid cascade hypothesis characterizes the stereotyped progression of pathological changes in Alzheimer's disease (AD) beginning with beta amyloid deposition, but does not address the reasons for amyloid deposition. Brain areas with relatively higher neuronal activity, metabolic demand, and production of reactive oxygen species in earlier life may have higher beta amyloid deposition in later life. The aim of this study was to investigate early life patterns of perfusion and late life patterns of amyloid deposition to determine the extent to which normative cerebral perfusion predisposes specific regions to future beta amyloid deposition. Materials and Methods: One hundred twenty-eight healthy, older human subjects (age: 56–87 years old; 44% women) underwent positron emission tomography (PET) imaging with [11C]PiB for measures of amyloid burden. Cerebral perfusion maps derived from 47 healthy younger adults (age: 22–49; 47%) who had undergone single photon emission computed tomography (SPECT) imaging, were averaged to create a normative template, representative of young, healthy adults. Perfusion and amyloid measures were investigated in 31 cortical regions from the Hammers atlas. We examined the spatial relationship between normative perfusion patterns and amyloid pathophysiology. Results: The pattern of increasing perfusion (temporal lobe<parietal lobe<frontal lobe<insula/cingulate gyrus<occipital lobe; F(4,26)=7.8, p = 0.0003) in young, healthy adults was not exactly identical to but approximated the pattern of increasing amyloid burden (temporal lobe<occipital lobe<frontal lobe<parietal lobe<insula/cingulate gyrus; F(4,26)=5.0, p = 0.004) in older adults. However, investigating subregions within cortical lobes provided consistent agreement between ranked normative perfusion patterns and expected Thal staging of amyloid progression in AD (Spearman r = 0.39, p = 0.03). Conclusion: Our findings suggest that brain areas with normatively greater perfusion may be more susceptible to amyloid deposition in later life, possibly due to higher metabolic demand, and associated levels of oxidative stress and inflammation. |
| first_indexed | 2024-04-11T01:58:02Z |
| format | Article |
| id | doaj.art-fcc1603aeac24327962386aa041d5061 |
| institution | Directory Open Access Journal |
| issn | 2666-2450 |
| language | English |
| last_indexed | 2024-04-11T01:58:02Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cerebral Circulation - Cognition and Behavior |
| spelling | doaj.art-fcc1603aeac24327962386aa041d50612023-01-03T04:53:18ZengElsevierCerebral Circulation - Cognition and Behavior2666-24502020-01-011100001Brain areas with normatively greater cerebral perfusion in early life may be more susceptible to beta amyloid deposition in late lifeIrene B. Meier0Patrick J. Lao1Anton Gietl2Robert S. Vorburger3José Gutierrez4Christopher M. Holland5Charles R.G. Guttmann6Dominik S. Meier7Alfred Buck8Roger M. Nitsch9Christoph Hock10Paul G. Unschuld11Adam M. Brickman12Institute for Regenerative Medicine IREM, University of Zurich, 8952 Zurich, Switzerland; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Corresponding author at: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, 630 West 168th Street, PS 16, New York, NY 10032.Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USAInstitute for Regenerative Medicine IREM, University of Zurich, 8952 Zurich, SwitzerlandTaub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USADepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USACarolina Neurosurgery & Spine Associates, Charlotte, NC 28204, USACenter for Neurological Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston MA 02215, USACenter for Neurological Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston MA 02215, USAUniversity Hospital Zurich, Clinic for Nuclear Medicine, Zurich, 8091, SwitzerlandInstitute for Regenerative Medicine IREM, University of Zurich, 8952 Zurich, SwitzerlandInstitute for Regenerative Medicine IREM, University of Zurich, 8952 Zurich, SwitzerlandInstitute for Regenerative Medicine IREM, University of Zurich, 8952 Zurich, SwitzerlandTaub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USABackground: The amyloid cascade hypothesis characterizes the stereotyped progression of pathological changes in Alzheimer's disease (AD) beginning with beta amyloid deposition, but does not address the reasons for amyloid deposition. Brain areas with relatively higher neuronal activity, metabolic demand, and production of reactive oxygen species in earlier life may have higher beta amyloid deposition in later life. The aim of this study was to investigate early life patterns of perfusion and late life patterns of amyloid deposition to determine the extent to which normative cerebral perfusion predisposes specific regions to future beta amyloid deposition. Materials and Methods: One hundred twenty-eight healthy, older human subjects (age: 56–87 years old; 44% women) underwent positron emission tomography (PET) imaging with [11C]PiB for measures of amyloid burden. Cerebral perfusion maps derived from 47 healthy younger adults (age: 22–49; 47%) who had undergone single photon emission computed tomography (SPECT) imaging, were averaged to create a normative template, representative of young, healthy adults. Perfusion and amyloid measures were investigated in 31 cortical regions from the Hammers atlas. We examined the spatial relationship between normative perfusion patterns and amyloid pathophysiology. Results: The pattern of increasing perfusion (temporal lobe<parietal lobe<frontal lobe<insula/cingulate gyrus<occipital lobe; F(4,26)=7.8, p = 0.0003) in young, healthy adults was not exactly identical to but approximated the pattern of increasing amyloid burden (temporal lobe<occipital lobe<frontal lobe<parietal lobe<insula/cingulate gyrus; F(4,26)=5.0, p = 0.004) in older adults. However, investigating subregions within cortical lobes provided consistent agreement between ranked normative perfusion patterns and expected Thal staging of amyloid progression in AD (Spearman r = 0.39, p = 0.03). Conclusion: Our findings suggest that brain areas with normatively greater perfusion may be more susceptible to amyloid deposition in later life, possibly due to higher metabolic demand, and associated levels of oxidative stress and inflammation.http://www.sciencedirect.com/science/article/pii/S2666245020300015Cerebral perfusionamyloidAlzheimer's disease |
| spellingShingle | Irene B. Meier Patrick J. Lao Anton Gietl Robert S. Vorburger José Gutierrez Christopher M. Holland Charles R.G. Guttmann Dominik S. Meier Alfred Buck Roger M. Nitsch Christoph Hock Paul G. Unschuld Adam M. Brickman Brain areas with normatively greater cerebral perfusion in early life may be more susceptible to beta amyloid deposition in late life Cerebral Circulation - Cognition and Behavior Cerebral perfusion amyloid Alzheimer's disease |
| title | Brain areas with normatively greater cerebral perfusion in early life may be more susceptible to beta amyloid deposition in late life |
| title_full | Brain areas with normatively greater cerebral perfusion in early life may be more susceptible to beta amyloid deposition in late life |
| title_fullStr | Brain areas with normatively greater cerebral perfusion in early life may be more susceptible to beta amyloid deposition in late life |
| title_full_unstemmed | Brain areas with normatively greater cerebral perfusion in early life may be more susceptible to beta amyloid deposition in late life |
| title_short | Brain areas with normatively greater cerebral perfusion in early life may be more susceptible to beta amyloid deposition in late life |
| title_sort | brain areas with normatively greater cerebral perfusion in early life may be more susceptible to beta amyloid deposition in late life |
| topic | Cerebral perfusion amyloid Alzheimer's disease |
| url | http://www.sciencedirect.com/science/article/pii/S2666245020300015 |
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