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Wall, Anders
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Publications (10 of 53) Show all publications
(2018). [15O]-H2O-PET in Premenstrual Dysphoria.
Open this publication in new window or tab >>[15O]-H2O-PET in Premenstrual Dysphoria
2018 (English)Other (Other (popular science, discussion, etc.))
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-335001 (URN)
Note

Dataset till en artikel:

Eriksson, O, Wall, A, Olsson, U, Marteinsdottir, I, Holstad, M, Ågren, H, Hartvig, P, Långström, B, Naessén, T. "Women with Premenstrual Dysphoria show signs of an Asymmetric Frontal Brain Activity with R > L in both Phases of the Menstrual Cycle" (submitted March 2018).

Available from: 2017-11-29 Created: 2017-11-29 Last updated: 2018-03-16Bibliographically approved
Leuzy, A., Rodriguez-Vieitez, E., Saint-Aubert, L., Chiotis, K., Almkvist, O., Savitcheva, I., . . . Nordberg, A. (2018). Longitudinal uncoupling of cerebral perfusion, glucose metabolism, and tau deposition in Alzheimer's disease.. Alzheimer's & Dementia, 14(5), 652-663
Open this publication in new window or tab >>Longitudinal uncoupling of cerebral perfusion, glucose metabolism, and tau deposition in Alzheimer's disease.
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2018 (English)In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 5, p. 652-663Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Cross-sectional findings using the tau tracer [18F]THK5317 (THK5317) have shown that [18F]fluorodeoxyglucose (FDG) positron emission tomography data can be approximated using perfusion measures (early-frame standardized uptake value ratio; ratio of tracer delivery in target to reference regions). In this way, a single positron emission tomography study can provide both functional and molecular information.

METHODS: We included 16 patients with Alzheimer's disease who completed follow-up THK5317 and FDG studies 17 months after baseline investigations. Linear mixed-effects models and annual percentage change maps were used to examine longitudinal change.

RESULTS: Limited spatial overlap was observed between areas showing declines in THK5317 perfusion measures and FDG. Minimal overlap was seen between areas showing functional change and those showing increased retention of THK5317.

DISCUSSION: Our findings suggest a spatiotemporal offset between functional changes and tau pathology and a partial uncoupling between perfusion and metabolism, possibly as a function of Alzheimer's disease severity.

Keywords
Alzheimer's disease, Alzheimer's disease dementia, FDG, Hypometabolism, Longitudinal study, Mild cognitive impairment, Neurofibrillary tangles, Perfusion SUVR, Perfusion imaging, Positron emission tomography (PET), Prodromal Alzheimer's disease, R(1), THK5317, Tau imaging
National Category
Radiology, Nuclear Medicine and Medical Imaging Medicinal Chemistry Neurosciences
Identifiers
urn:nbn:se:uu:diva-337704 (URN)10.1016/j.jalz.2017.11.008 (DOI)000432438800009 ()29268078 (PubMedID)
Funder
Swedish Research Council, 05817Swedish Foundation for Strategic Research Gun och Bertil Stohnes StiftelseThe Karolinska Institutet's Research FoundationThe Swedish Brain FoundationWenner-Gren Foundations
Available from: 2018-01-03 Created: 2018-01-03 Last updated: 2018-08-01Bibliographically approved
Thordardottir, S., Rodriguez-Vieitez, E., Almkvist, O., Ferreira, D., Saint-Aubert, L., Kinhult-Stahlbom, A., . . . Graff, C. (2018). Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study. Alzheimer's Research & Therapy, 10, Article ID 45.
Open this publication in new window or tab >>Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study
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2018 (English)In: Alzheimer's Research & Therapy, ISSN 0065-6755, E-ISSN 1758-9193, Vol. 10, article id 45Article in journal (Refereed) Published
Abstract [en]

Background: The range of onset ages within some PSEN1 families is wide, and a few cases of reduced penetrance of PSEN1 mutations have been reported. However, published data on reduced penetrance have been limited to clinical histories, often collected retrospectively and lacking biomarker information. We present a case of reduced penetrance of the PSEN1 H163Y mutation in a carrier prospectively followed for 22 years.

Methods: Two brothers (A and B), both carriers of the H163Y mutation, were followed between 1995 and 2017. They underwent repeated clinical evaluations, neuropsychological assessments, and cerebrospinal fluid analyses, as well as brain imaging examinations with structural magnetic resonance, [18F]fluorodeoxyglucose positron emission tomography, and [11C]Pittsburgh compound B positron emission tomography.

Results: Brother A was followed between 44 and 64 years of age. Cognitive symptoms due to Alzheimer’s disease set in at the age of 54. Gradual worsening of symptoms resulted in admittance to a nursing home owing to dependence on others for all activities of daily living. He showed a curvilinear decline in cognitive function on neuropsychological tests, and changes on magnetic resonance imaging, positron emission tomography, and biomarkers in the cerebrospinal fluid supported a clinical diagnosis of Alzheimer’s disease. Brother A died at the age of 64 and fulfilled the criteria for definitive Alzheimer’s disease according to neuropathological examination results. Brother B was followed between the ages of 43 and 65 and showed no cognitive deterioration on repeated neuropsychological test occasions. In addition, no biomarker evidence of Alzheimer’s disease pathology was detected, either on imaging examinations or in cerebrospinal fluid.

Conclusions: The average (SD) age of symptom onset for PSEN1 H163Y is 51 ± 7 years according to previous studies. However, we present a case of a biomarker-verified reduction in penetrance in a mutation carrier who was still symptom-free at the age of 65. This suggests that other genetic, epigenetic, and/or environmental factors modify the onset age.

Keywords
Autosomal dominant Alzheimer's disease, CSF, [F-18]fluorodeoxyglucose PET, [C-11]Pittsburgh compound B PET, Reduced penetrance
National Category
Geriatrics
Identifiers
urn:nbn:se:uu:diva-356491 (URN)10.1186/s13195-018-0374-y (DOI)000431827700001 ()29747683 (PubMedID)
Funder
Swedish Research Council, 05817Swedish Foundation for Strategic Research Knut and Alice Wallenberg FoundationStockholm County CouncilGun och Bertil Stohnes StiftelseStiftelsen Gamla TjänarinnorÅke Wiberg Foundation
Available from: 2018-07-30 Created: 2018-07-30 Last updated: 2018-07-30Bibliographically approved
Iaccarino, L., Chiotis, K., Alongi, P., Almkvist, O., Wall, A., Cerami, C., . . . Perani, D. (2017). A Cross-Validation of FDG- and Amyloid-PET Biomarkers in Mild Cognitive Impairment for the Risk Prediction to Dementia due to Alzheimer's Disease in a Clinical Setting. Journal of Alzheimer's Disease, 59(2), 603-614
Open this publication in new window or tab >>A Cross-Validation of FDG- and Amyloid-PET Biomarkers in Mild Cognitive Impairment for the Risk Prediction to Dementia due to Alzheimer's Disease in a Clinical Setting
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2017 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 59, no 2, p. 603-614Article in journal (Refereed) Published
Abstract [en]

Assessments of brain glucose metabolism (F-18-FDG-PET) and cerebral amyloid burden (C-11-PiB-PET) in mild cognitive impairment (MCI) have shown highly variable performances when adopted to predict progression to dementia due to Alzheimer's disease (ADD). This study investigates, in a clinical setting, the separate and combined values of F-18-FDGPET and C-11-PiB-PET in ADD conversion prediction with optimized data analysis procedures. Respectively, we investigate the accuracy of an optimized SPM analysis for F-18-FDG-PET and of standardized uptake value ratio semiquantification for C-11-PiB-PET in predicting ADD conversion in 30 MCI subjects (age 63.57 +/- 7.78 years). Fourteen subjects converted to ADD during the follow-up (median 26.5 months, inter-quartile range 30 months). Receiver operating characteristic analyses showed an area under the curve (AUC) of 0.89 and of 0.81 for, respectively, F-18-FDG-PET and C-11-PiB-PET. F-18-FDG-PET, compared to C-11-PiB-PET, showed higher specificity (1.00 versus 0.62, respectively), but lower sensitivity (0.79 versus 1.00). Combining the biomarkers improved classification accuracy (AUC = 0.96). During the follow-up time, all the MCI subjects positive for both PET biomarkers converted to ADD, whereas all the subjects negative for both remained stable. The difference in survival distributions was confirmed by a log-rank test (p = 0.002). These results indicate a very high accuracy in predicting MCI to ADD conversion of both F-18-FDG-PET and C-11-PiB-PET imaging, the former showing optimal performance based on the SPM optimized parametric assessment. Measures of brain glucose metabolism and amyloid load represent extremely powerful diagnostic and prognostic biomarkers with complementary roles in prodromal dementia phase, particularly when tailored to individual cases in clinical settings.

Keywords
Alzheimer's disease, C-11-PiB-PET, conversion prediction, dementia, early diagnosis, F-18-FDG-PET, mild cognitive impairment, prognosis
National Category
Neurology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-331961 (URN)10.3233/JAD-170158 (DOI)000405805400019 ()
Funder
EU, FP7, Seventh Framework Programme, 278850, HEALTH-F2-2011278850Swedish Research Council, 05817Swedish Foundation for Strategic Research The Swedish Brain FoundationWenner-Gren Foundations
Available from: 2017-10-20 Created: 2017-10-20 Last updated: 2017-10-20Bibliographically approved
Rodriguez-Vieitez, E., Leuzy, A., Chiotis, K., Saint-Aubert, L., Wall, A. & Nordberg, A. (2017). Comparability of [F-18]THK5317 and [C-11]PIB blood flow proxy images with [F-18]FDG positron emission tomography in Alzheimer's disease. Journal of Cerebral Blood Flow and Metabolism, 37(2), 740-749
Open this publication in new window or tab >>Comparability of [F-18]THK5317 and [C-11]PIB blood flow proxy images with [F-18]FDG positron emission tomography in Alzheimer's disease
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2017 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, no 2, p. 740-749Article in journal (Refereed) Published
Abstract [en]

For amyloid positron emission tomography tracers, the simplified reference tissue model derived ratio of influx rate in target relative to reference region (R-1) has been shown to serve as a marker of brain perfusion, and, due to the strong coupling between perfusion and metabolism, as a proxy for glucose metabolism. In the present study, 11 prodromal Alzheimer's disease and nine Alzheimer's disease dementia patients underwent [F-18]THK5317, carbon-11 Pittsburgh Compound-B ([C-11]PIB), and 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) positron emission tomography to assess the possible use of early-phase [F-18]THK5317 and R-1 as proxies for brain perfusion, and thus, for glucose metabolism. Discriminative performance (prodromal vs Alzheimer's disease dementia) of [F-18]THK5317 (early-phase SUVr and R-1) was compared with that of [C-11]PIB (early-phase SUVr and R-1) and [F-18]FDG. Strong positive correlations were found between [F-18]THK5317 (early-phase, R-1) and [F-18]FDG, particularly in frontal and temporoparietal regions. Differences in correlations between early-phase and R-1 ([F-18]THK5317 and [C-11]PIB) and [F-18]FDG, were not statistically significant, nor were differences in area under the curve values in the discriminative analysis. Our findings suggest that early-phase [F-18]THK5317 and R-1 provide information on brain perfusion, closely related to glucose metabolism. As such, a single positron emission tomography study with [F-18]THK5317 may provide information about both tau pathology and brain perfusion in Alzheimer's disease, with potential clinical applications.

Place, publisher, year, edition, pages
SAGE PUBLICATIONS INC, 2017
Keywords
Alzheimer's disease, early-phase carbon-11 Pittsburgh Compound-B, early-phase [F-18]THK5317 positron emission tomography, 2-deoxy-2-[F-18]fluoro-D-glucose, simplified reference tissue model R-1
National Category
Endocrinology and Diabetes Hematology Neurology
Identifiers
urn:nbn:se:uu:diva-319114 (URN)10.1177/0271678X16645593 (DOI)000393903900029 ()27107028 (PubMedID)
Funder
Swedish Research Council, 05817Swedish Foundation for Strategic Research The Karolinska Institutet's Research FoundationThe Swedish Brain FoundationThe Dementia Association - The National Association for the Rights of the DementedEU, European Research Council, HEALTH-F2-2011-278850Stiftelsen Gamla TjänarinnorWenner-Gren Foundations
Available from: 2017-04-03 Created: 2017-04-03 Last updated: 2017-11-29Bibliographically approved
Vedung, F., Antoni, G., Wall, A., Fahlström, M., Larsson, E.-M. & Marklund, N. (2017). Persistent Decrease Of Cerebral Blood Flow In Traumatic Brain Injury And Sports-Related Concussion. Paper presented at 35th Annual National Neurotrauma Symposium, JUL 07-12, 2017, Snowbird, UT. Journal of Neurotrauma, 34(13), A8-A9
Open this publication in new window or tab >>Persistent Decrease Of Cerebral Blood Flow In Traumatic Brain Injury And Sports-Related Concussion
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2017 (English)In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 34, no 13, p. A8-A9Article in journal, Meeting abstract (Other academic) Published
Keywords
Cerebral perfusion, Concussion, ASL, athletes
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-335815 (URN)10.1089/neu.2017.29011.abstracts (DOI)000404530400021 ()
Conference
35th Annual National Neurotrauma Symposium, JUL 07-12, 2017, Snowbird, UT
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2018-01-22 Created: 2018-01-22 Last updated: 2018-01-22Bibliographically approved
Bodén, R., Persson, J., Wall, A., Lubberink, M., Ekselius, L., Larsson, E.-M. & Antoni, G. (2017). Striatal Phosphodiesterase 10A and Medial Prefrontal Cortical Thickness in Patients with Schizophrenia: A PET and MRI Study. Paper presented at 72nd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), MAY 18-20, 2017, San Diego, CA. Biological Psychiatry, 81(10), S386-S387
Open this publication in new window or tab >>Striatal Phosphodiesterase 10A and Medial Prefrontal Cortical Thickness in Patients with Schizophrenia: A PET and MRI Study
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2017 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, no 10, p. S386-S387Article in journal, Meeting abstract (Other academic) Published
Keywords
Schizophrenia, Positron Emission Tomography, Magnetic resonance imaging, striatum, Cortical Thickness
National Category
Psychiatry Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-331804 (URN)10.1016/j.biopsych.2017.02.681 (DOI)000400348701048 ()
Conference
72nd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), MAY 18-20, 2017, San Diego, CA
Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2017-10-18Bibliographically approved
Bodén, R., Persson, J., Wall, A., Lubberink, M., Ekselius, L., Larsson, E.-M. & Antoni, G. (2017). Striatal phosphodiesterase 10A and medial prefrontal cortical thickness in patients with schizophrenia: a PET and MRI study. Translational Psychiatry, 7(3), Article ID e1050.
Open this publication in new window or tab >>Striatal phosphodiesterase 10A and medial prefrontal cortical thickness in patients with schizophrenia: a PET and MRI study
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2017 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 7, no 3, article id e1050Article in journal (Refereed) Published
Abstract [en]

The enzyme phosphodiesterase 10A (PDE10A) is abundant in striatal medium spiny neurons and has been implicated in the pathophysiology of schizophrenia in animal models and is investigated as a possible new pharmacological treatment target. A reduction of prefrontal cortical thickness is common in schizophrenia, but how this relates to PDE10A expression is unknown. Our study aim was to compare, we believe for the first time, the striatal non-displaceable binding potential (BPND) of the new validated PDE10A ligand [(11)C]Lu AE92686 between patients with schizophrenia and healthy controls. Furthermore, we aimed to assess the correlation of PDE10A BPND to cortical thickness. Sixteen healthy male controls and 10 male patients with schizophrenia treated with clozapine, olanzapine or quetiapine were investigated with positron emission tomography (PET) and magnetic resonance imaging (MRI). Striatal binding potential (BPND) of [(11)C]Lu AE92686 was acquired through dynamic PET scans and cortical thickness by structural MRI. Clinical assessments of symptoms and cognitive function were performed and the antipsychotic dosage was recorded. Patients with schizophrenia had a significantly lower BPND of [(11)C]Lu AE92686 in striatum (P=0.003) than healthy controls. The striatal BPND significantly correlated to cortical thickness in the medial prefrontal cortex and superior frontal gyrus across patients with schizophrenia and healthy controls. No significant correlation was observed between the BPND for [(11)C]Lu AE92686 in striatum and age, schizophrenia symptoms, antipsychotic dosage, coffee consumption, smoking, duration of illness or cognitive function in the patients. In conclusion, PDE10A may be important for functioning in the striato-cortical interaction and in the pathophysiology of schizophrenia.

National Category
Psychiatry Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-316901 (URN)10.1038/tp.2017.11 (DOI)000397228200002 ()28267149 (PubMedID)
Funder
Swedish Research Council, 2016-02362
Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2018-01-13Bibliographically approved
Rodriguez-Vieitez, E., Carter, S. F., Chiotis, K., Saint-Aubert, L., Leuzy, A., Scholl, M., . . . Nordberg, A. (2016). Comparison of Early-Phase C-11-Deuterium-L-Deprenyl and C-11-Pittsburgh Compound B PET for Assessing Brain Perfusion in Alzheimer Disease. Journal of Nuclear Medicine, 57(7), 1071-1077
Open this publication in new window or tab >>Comparison of Early-Phase C-11-Deuterium-L-Deprenyl and C-11-Pittsburgh Compound B PET for Assessing Brain Perfusion in Alzheimer Disease
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2016 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 57, no 7, p. 1071-1077Article in journal (Refereed) Published
Abstract [en]

The PET tracer C-11-deuterium-L-deprenyl (C-11-DED) has been used to visualize activated astrocytes in vivo in patients with Alzheimer disease (AD). In this multitracer PET study, early-phase C-11-DED and C-11-Pittsburgh compound B (C-11-PiB) (eDED and ePiB, respectively) were compared as surrogate markers of brain perfusion, and the extent to which C-11-DED binding is influenced by brain perfusion was investigated. METHODS: C-11-DED, C-11-PiB, and F-18-FDG dynamic PET scans were obtained in age-matched groups comprising AD patients (n = 8), patients with mild cognitive impairment (n = 17), and healthy controls (n = 16). A modified reference Patlak model was used to quantify C-11-DED binding. A simplified reference tissue model was applied to both C-11-DED and C-11-PiB to measure brain perfusion relative to the cerebellar gray matter (R-1) and binding potentials. C-11-PiB retention and F-18-FDG uptake were also quantified as target-to-pons SUV ratios in 12 regions of interest (ROIs). RESULTS: The strongest within-subject correlations with the corresponding R-1 values (R-1,R-DED and R-1,R-PiB, respectively) and with F-18-FDG uptake were obtained when the eDED and ePiB PET data were measured 1-4 min after injection. The optimum eDED/ePiB intervals also showed strong, significant ROI-based intersubject Pearson correlations with R-1,R-DED/R-1,R-PiB and with F-18-FDG uptake, whereas C-11-DED binding was largely independent of brain perfusion, as measured by eDED. Corresponding voxelwise correlations confirmed the ROI-based results. Temporoparietal eDED or ePiB brain perfusion measurements were highly discriminative between patient and control groups, with discriminative ability statistically comparable to that of temporoparietal F-18-FDG glucose metabolism. Hypometabolism extended over wider regions than hypoperfusion in patient groups compared with controls. CONCLUSION: The 1- to 4-min early-frame intervals of C-11-DED or C-11-PiB are suitable surrogate measures for brain perfusion. C-11-DED binding is independent of brain perfusion, and thus C-11-DED PET can provide information on both functional (brain perfusion) and pathologic (astrocytosis) aspects from a single PET scan. In comparison with glucose metabolism, early-phase C-11-DED and C-11-PiB perfusion appear to provide complementary rather than redundant information.

Keywords
amyloid, astrocytosis, brain perfusion, early-phase PET
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-300056 (URN)10.2967/jnumed.115.168732 (DOI)000378979200016 ()26912447 (PubMedID)
Funder
Swedish Research Council, 05817Swedish Foundation for Strategic Research Knut and Alice Wallenberg FoundationThe Karolinska Institutet's Research FoundationThe Swedish Brain FoundationThe Dementia Association - The National Association for the Rights of the DementedEU, FP7, Seventh Framework ProgrammeStiftelsen Gamla TjänarinnorWenner-Gren Foundations
Available from: 2016-08-02 Created: 2016-08-02 Last updated: 2017-11-28Bibliographically approved
Rodriguez-Vieitez, E., Saint-Aubert, L., Carter, S. F., Almkvist, O., Farid, K., Scholl, M., . . . Nordberg, A. (2016). Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer's disease. Brain, 139(3), 922-936
Open this publication in new window or tab >>Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer's disease
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2016 (English)In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 139, no 3, p. 922-936Article in journal (Refereed) Published
Abstract [en]

The relationships between pathophysiological processes in Alzheimer's disease remain largely unclear. In a longitudinal, multitracer PET study, Rodriguez-Vieitez et al. reveal that progression of autosomal dominant Alzheimer's disease is accompanied by prominent early and then declining astrocytosis, increasing amyloid plaque deposition and decreasing glucose metabolism. Astrocyte activation may initiate Alzheimer pathology.See Schott and Fox (doi: 10.1093/brain/awv405) for a scientific commentary on this article. The relationships between pathophysiological processes in Alzheimer's disease remain largely unclear. In a longitudinal, multitracer PET study, Rodriguez-Vieitez et al. reveal that progression of autosomal dominant Alzheimer's disease is accompanied by prominent early and then declining astrocytosis, increasing amyloid plaque deposition and decreasing glucose metabolism. Astrocyte activation may initiate Alzheimer pathology.Alzheimer's disease is a multifactorial dementia disorder characterized by early amyloid-beta, tau deposition, glial activation and neurodegeneration, where the interrelationships between the different pathophysiological events are not yet well characterized. In this study, longitudinal multitracer positron emission tomography imaging of individuals with autosomal dominant or sporadic Alzheimer's disease was used to quantify the changes in regional distribution of brain astrocytosis (tracer C-11-deuterium-L-deprenyl), fibrillar amyloid-beta plaque deposition (C-11-Pittsburgh compound B), and glucose metabolism (F-18-fluorodeoxyglucose) from early presymptomatic stages over an extended period to clinical symptoms. The 52 baseline participants comprised autosomal dominant Alzheimer's disease mutation carriers (n = 11; 49.6 +/- 10.3 years old) and non-carriers (n = 16; 51.1 +/- 14.2 years old; 10 male), and patients with sporadic mild cognitive impairment (n = 17; 61.9 +/- 6.4 years old; nine male) and sporadic Alzheimer's disease (n = 8; 63.0 +/- 6.5 years old; five male); for confidentiality reasons, the gender of mutation carriers is not revealed. The autosomal dominant Alzheimer's disease participants belonged to families with known mutations in either presenilin 1 (PSEN1) or amyloid precursor protein (APPswe or APParc) genes. Sporadic mild cognitive impairment patients were further divided into C-11-Pittsburgh compound B-positive (n = 13; 62.0 +/- 6.4; seven male) and C-11-Pittsburgh compound B-negative (n = 4; 61.8 +/- 7.5 years old; two male) groups using a neocortical standardized uptake value ratio cut-off value of 1.41, which was calculated with respect to the cerebellar grey matter. All baseline participants underwent multitracer positron emission tomography scans, cerebrospinal fluid biomarker analysis and neuropsychological assessment. Twenty-six of the participants underwent clinical and imaging follow-up examinations after 2.8 +/- 0.6 years. By using linear mixed-effects models, fibrillar amyloid-beta plaque deposition was first observed in the striatum of presymptomatic autosomal dominant Alzheimer's disease carriers from 17 years before expected symptom onset; at about the same time, astrocytosis was significantly elevated and then steadily declined. Diverging from the astrocytosis pattern, amyloid-beta plaque deposition increased with disease progression. Glucose metabolism steadily declined from 10 years after initial amyloid-beta plaque deposition. Patients with sporadic mild cognitive impairment who were C-11-Pittsburgh compound B-positive at baseline showed increasing amyloid-beta plaque deposition and decreasing glucose metabolism but, in contrast to autosomal dominant Alzheimer's disease carriers, there was no significant longitudinal decline in astrocytosis over time. The prominent initially high and then declining astrocytosis in autosomal dominant Alzheimer's disease carriers, contrasting with the increasing amyloid-beta plaque load during disease progression, suggests astrocyte activation is implicated in the early stages of Alzheimer's disease pathology.

Keywords
astrocytosis, autosomal dominant Alzheimer's disease, C-11-deuterium-L-deprenyl, F-18-fluorodeoxyglucose, C-11-Pittsburgh compound B
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-282820 (URN)10.1093/brain/awv404 (DOI)000371694600031 ()26813969 (PubMedID)
Funder
Swedish Research Council, 05817Swedish Foundation for Strategic Research Knut and Alice Wallenberg FoundationStockholm County CouncilThe Swedish Brain FoundationThe Dementia Association - The National Association for the Rights of the DementedEU, European Research CouncilStiftelsen Gamla TjänarinnorWenner-Gren Foundations
Available from: 2016-04-07 Created: 2016-04-07 Last updated: 2017-11-30Bibliographically approved
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