A multi-tracer PET approach to study early-onset familial and sporadic Alzheimer's disease
Cumulated scientific evidence suggests that the pathology causing Alzheimer's disease (AD) occurs many years or even decades before memory impairment and other clinical symptoms arise. Tangible and detailed knowledge about different pathological processes, their interactions, and time course is...
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Inst för neurobiologi, vårdvetenskap och samhälle / Dept of Neurobiology, Care Sciences and Society
2011
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ftkarolinskainst:oai:openarchive.ki.se:10616/40696 2023-05-15T14:28:12+02:00 A multi-tracer PET approach to study early-onset familial and sporadic Alzheimer's disease Schöll, Michael 2011-09-16 application/pdf http://hdl.handle.net/10616/40696 eng eng Inst för neurobiologi, vårdvetenskap och samhälle / Dept of Neurobiology, Care Sciences and Society I. Schöll M, Almkvist O, Axelman K, Stefanova E, Wall A, Westman E, Långström B, Lannfelt L, Graff C, Nordberg A. Glucose metabolism and PIB binding in carriers of a His163Tyr presenilin 1 mutation. Neurobiol Aging. 2011 Aug;32(8):1388-99. Epub 2009 Sep 30. ::pmid::19796846 ::doi::10.1016/j.neurobiolaging.2009.08.016 ::isi::000293028500004 II. Schöll M, Almkvist O, Bogdanovic N, Wall A, Långström B, Viitanen M, Nordberg A. Time course of glucose metabolism in relation to cognitive performance and postmortem neuropathology in Met146Val PSEN1 mutation carriers. J Alzheimers Dis. 2011 Jan 1;24(3):495-506. ::pmid::21297272 ::doi::10.3233/JAD-2011-101563 ::isi::000292496900007 III. Schöll M, Wall A, Thordardottir S, Ferreira D, Bogdanovic N, Rasmuson S, Byström A, Långström B, Almkvist O, Graff C, Nordberg A. Low PIB PET retention in presence of pathological CSF biomarkers in Arctic APP mutation carriers. [Submitted] IV. Carter SF, Schöll M, Almkvist O, Wall A, Engler H, Långström B, Nordberg A. Evidence for astrocytosis in prodromal Alzheimer's disease provided by 11C-Deuterium-LDeprenyl - A multi-tracer PET paradigm combining 11C-PIB and 18F-FDG. [Accepted] ::pmid::22213821 ::isi::000298660900018 978-91-7457-458-6 http://hdl.handle.net/10616/40696 info:eu-repo/semantics/openAccess info:eu-repo/semantics/doctoralThesis dok 2011 ftkarolinskainst 2022-10-05T22:33:50Z Cumulated scientific evidence suggests that the pathology causing Alzheimer's disease (AD) occurs many years or even decades before memory impairment and other clinical symptoms arise. Tangible and detailed knowledge about different pathological processes, their interactions, and time course is therefore of the essence both for the development of potentially successful treatments and a reliable early diagnosis of this relentless disorder. The past decade has thus seen an explosion in research on biomarkers that could provide in vivo evidence for these pathological processes, involving β-amyloid (Aβ) production and aggregation into plaques, neurofibrillary tangle formation, neuroinflammation, and eventually neurodegeneration. The rare form of dominantly-inherited early-onset familial AD (eoFAD), with almost complete mutation penetrance and defined age of disease onset, has been proposed as a model to study the very early disease mechanisms that are also supposed to underlie the common sporadic form (sAD). However, more than 200 mutations in three different genes (PSEN1 and 2, APP) have been identified as causing eoFAD, some of which have been shown to differ substantially from others. This work employed multi-tracer positron emission tomography (PET), using the tracers 2-[18F]‐fluoro-2‐deoxy‐D‐glucose (FDG), N-methyl-[11C] 2-(4'- methylaminophenyl)-6-hydroxy-benzothiazole (PIB), and [11C]-L-deuterium-deprenyl (DED) to explore the characteristics, time course and interrelationship of cerebral glucose metabolism, fibrillar Aβ burden, and astrocyte activation (astrocytosis) at different presymptomatic and symptomatic disease stages of eoFAD and sAD, in relationship to cognition, other AD biomarkers, and/or post-mortem pathology. Thalamic hypometabolism in PSEN1 eoFAD mutation carriers was demonstrated in this thesis nearly 20 years before they were expected to develop clinical symptoms. The pattern of hypometabolism studied in several mutation carriers spread subsequently to regions that are also typically affected ... Doctoral or Postdoctoral Thesis Arctic Karolinska Institutet: Publications |
institution |
Open Polar |
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Karolinska Institutet: Publications |
op_collection_id |
ftkarolinskainst |
language |
English |
description |
Cumulated scientific evidence suggests that the pathology causing Alzheimer's disease (AD) occurs many years or even decades before memory impairment and other clinical symptoms arise. Tangible and detailed knowledge about different pathological processes, their interactions, and time course is therefore of the essence both for the development of potentially successful treatments and a reliable early diagnosis of this relentless disorder. The past decade has thus seen an explosion in research on biomarkers that could provide in vivo evidence for these pathological processes, involving β-amyloid (Aβ) production and aggregation into plaques, neurofibrillary tangle formation, neuroinflammation, and eventually neurodegeneration. The rare form of dominantly-inherited early-onset familial AD (eoFAD), with almost complete mutation penetrance and defined age of disease onset, has been proposed as a model to study the very early disease mechanisms that are also supposed to underlie the common sporadic form (sAD). However, more than 200 mutations in three different genes (PSEN1 and 2, APP) have been identified as causing eoFAD, some of which have been shown to differ substantially from others. This work employed multi-tracer positron emission tomography (PET), using the tracers 2-[18F]‐fluoro-2‐deoxy‐D‐glucose (FDG), N-methyl-[11C] 2-(4'- methylaminophenyl)-6-hydroxy-benzothiazole (PIB), and [11C]-L-deuterium-deprenyl (DED) to explore the characteristics, time course and interrelationship of cerebral glucose metabolism, fibrillar Aβ burden, and astrocyte activation (astrocytosis) at different presymptomatic and symptomatic disease stages of eoFAD and sAD, in relationship to cognition, other AD biomarkers, and/or post-mortem pathology. Thalamic hypometabolism in PSEN1 eoFAD mutation carriers was demonstrated in this thesis nearly 20 years before they were expected to develop clinical symptoms. The pattern of hypometabolism studied in several mutation carriers spread subsequently to regions that are also typically affected ... |
format |
Doctoral or Postdoctoral Thesis |
author |
Schöll, Michael |
spellingShingle |
Schöll, Michael A multi-tracer PET approach to study early-onset familial and sporadic Alzheimer's disease |
author_facet |
Schöll, Michael |
author_sort |
Schöll, Michael |
title |
A multi-tracer PET approach to study early-onset familial and sporadic Alzheimer's disease |
title_short |
A multi-tracer PET approach to study early-onset familial and sporadic Alzheimer's disease |
title_full |
A multi-tracer PET approach to study early-onset familial and sporadic Alzheimer's disease |
title_fullStr |
A multi-tracer PET approach to study early-onset familial and sporadic Alzheimer's disease |
title_full_unstemmed |
A multi-tracer PET approach to study early-onset familial and sporadic Alzheimer's disease |
title_sort |
multi-tracer pet approach to study early-onset familial and sporadic alzheimer's disease |
publisher |
Inst för neurobiologi, vårdvetenskap och samhälle / Dept of Neurobiology, Care Sciences and Society |
publishDate |
2011 |
url |
http://hdl.handle.net/10616/40696 |
genre |
Arctic |
genre_facet |
Arctic |
op_relation |
I. Schöll M, Almkvist O, Axelman K, Stefanova E, Wall A, Westman E, Långström B, Lannfelt L, Graff C, Nordberg A. Glucose metabolism and PIB binding in carriers of a His163Tyr presenilin 1 mutation. Neurobiol Aging. 2011 Aug;32(8):1388-99. Epub 2009 Sep 30. ::pmid::19796846 ::doi::10.1016/j.neurobiolaging.2009.08.016 ::isi::000293028500004 II. Schöll M, Almkvist O, Bogdanovic N, Wall A, Långström B, Viitanen M, Nordberg A. Time course of glucose metabolism in relation to cognitive performance and postmortem neuropathology in Met146Val PSEN1 mutation carriers. J Alzheimers Dis. 2011 Jan 1;24(3):495-506. ::pmid::21297272 ::doi::10.3233/JAD-2011-101563 ::isi::000292496900007 III. Schöll M, Wall A, Thordardottir S, Ferreira D, Bogdanovic N, Rasmuson S, Byström A, Långström B, Almkvist O, Graff C, Nordberg A. Low PIB PET retention in presence of pathological CSF biomarkers in Arctic APP mutation carriers. [Submitted] IV. Carter SF, Schöll M, Almkvist O, Wall A, Engler H, Långström B, Nordberg A. Evidence for astrocytosis in prodromal Alzheimer's disease provided by 11C-Deuterium-LDeprenyl - A multi-tracer PET paradigm combining 11C-PIB and 18F-FDG. [Accepted] ::pmid::22213821 ::isi::000298660900018 978-91-7457-458-6 http://hdl.handle.net/10616/40696 |
op_rights |
info:eu-repo/semantics/openAccess |
_version_ |
1766302366032723968 |