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- Lemoine, Laetitia, et al.
(författare)
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Amyloid, tau, and astrocyte pathology in autosomal-dominant Alzheimer's disease variants : A beta PParc and PSEN1DE9
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:10, s. 5609-5619
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Tidskriftsartikel (refereegranskat)abstract
- Autosomal-dominant Alzheimer's disease (ADAD) may be associated with atypical amyloid beta deposits in the brain. In vivo amyloid imaging using(11)C-Pittsburgh compound B (PiB) tracer has shown differences in binding between brains from ADAD and sporadic Alzheimer's disease (sAD) patients. To gain further insight into the various pathological characteristics of these genetic variants, we performed large frozen hemisphere autoradiography and brain homogenate binding assays with(3)H-PiB,H-3-MK6240-H-3-THK5117, and(3)H-deprenyl for detection of amyloid fibrils, tau depositions, and activated astrocytes, respectively, in twoA beta PParcmutation carriers, onePSEN1 Delta E9mutation carrier, and three sAD cases. The results were compared with Abeta 40, Abeta 42, AT8, and GFAP immunostaining, respectively, as well as with Congo red and Bielschowsky. PiB showed a very low binding inA beta PParc. A high binding was observed inPSEN1 Delta E9and in sAD tissues but with different binding patterns. Comparable(3)H-THK5117 and(3)H-deprenyl brain homogenate binding was observed forA beta PParc,PSEN1 Delta E9, and sAD, respectively. Some differences were observed between(3)H-MK6240 and(3)H-THK5117 in ADAD. A positive correlation between(3)H-deprenyl and(3)H-THK5117 binding was observed inA beta PParc, while no such correlation was found inPSEN1 Delta E9and sAD. Our study demonstrates differences in the properties of the amyloid plaques between two genetic variants of AD and sAD. Despite the lack of measurable amyloid fibrils by PiB in theA beta PParccases, high regional tau and astrocyte binding was observed. The lack of correlation between(3)H-deprenyl and(3)H-THK5117 binding inPSEN1 Delta E9and sAD in contrast of the positive correlation observed in theA beta PParccases suggest differences in the pathological cascade between variants of AD that warrant further exploration in vivo.
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| 2. |
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| 3. |
- Ni, Ruiqing, et al.
(författare)
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Amyloid tracers binding sites in autosomal dominant and sporadic Alzheimer's disease
- 2017
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 13:4, s. 419-430
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Amyloid imaging has been integrated into diagnostic criteria for Alzheimer's disease (AD). How amyloid tracers binding differ for different tracer structures and amyloid-beta aggregates in autosomal dominant AD (ADAD) and sporadic AD is unclear. Methods: Binding properties of different amyloid tracers were examined in brain homogenates from six ADAD with APPswe, PS1 M146V, and PS1 E Delta 9 mutations, 13 sporadic AD, and 14 control cases. Results: H-3-PIB, H-3-florbetaben, H-3-AZD2184, and BTA-1 shared a high-and a varying low-affinity binding site in the frontal cortex of sporadic AD. AZD2184 detected another binding site (affinity 33 nM) in the frontal cortex of ADAD. The H-3-AZD2184 and H-3-PIB binding were significantly higher in the striatum of ADAD compared to sporadic AD and control. Polyphenol resveratrol showed strongest inhibition on H-3-AZD84 binding followed by H-3-florbetaben and minimal on H-3-PIB. Discussion: This study implies amyloid tracers of different structures detect different sites on amyloid-beta fibrils or conformations.
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| 4. |
- Schöll, Michael, et al.
(författare)
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Time Course of Glucose Metabolism in Relation to Cognitive Performance and Postmortem Neuropathology in Met146Val PSEN1 Mutation Carriers
- 2011
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 24:3, s. 495-506
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Tidskriftsartikel (refereegranskat)abstract
- Studies in carriers of mutations that cause early-onset familial Alzheimer's disease (eoFAD) are of significant interest. We showed previously that regional glucose hypometabolism could be detected many years before disease onset in presenilin 1 (PSEN1) mutation carriers. Here we studied four members of a family with a Met146Val PSEN1 mutation, two symptomatic carriers and two non-carriers, longitudinally with (18)F-FDG PET over a period of about two and four years, respectively. The two mutation carriers showed global cortical glucose hypometabolism over time with the most distinct decline occurring in the posterior cingulate, the parietal and parietotemporal cortex, which was also observed when compared with a group of 23 healthy controls and a group of 27 sporadic Alzheimer's disease (sAD) patients. This decline correlated with cognitive deterioration over time as measured by neuropsychological tests. Postmortem examination of brain tissue revealed substantially elevated levels of AD type neuropathology in terms of neuritic plaques and neurofibrillary tangles in the two mutation carriers compared with a reference group of 249 sAD patients. In the mutation carriers, the amount of neuritic plaques but not neurofibrillary tangles correlated hereby significantly with regional glucose metabolism as measured by (18)F-FDG on the last scanning occasions, which were performed four and approximately five years before death, respectively. We here show that FDG PET can depict in vivo the aggressive disease progression in eoFAD mutation carriers in relationship to neuropathology.
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