Dataset Information

In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET.

ABSTRACT: INTRODUCTION:Synaptic loss is a robust and consistent pathology in Alzheimer's disease (AD) and the major structural correlate of cognitive impairment. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising biomarker of synaptic density. METHODS:We measured SV2A binding in 34 participants with early AD and 19 cognitively normal (CN) participants using [11 C]UCB-J PET and a cerebellar reference region for calculation of the distribution volume ratio. RESULTS:We observed widespread reductions of SV2A binding in medial temporal and neocortical brain regions in early AD compared to CN participants. These reductions were largely maintained after correction for volume loss and were more extensive than decreases in gray matter volume. CONCLUSION:We were able to measure widespread synaptic loss due to AD using [11 C]UCB-J PET. Future studies will continue to evaluate the utility of SV2A PET for tracking AD progression and for monitoring potential therapies.

SUBMITTER: Mecca AP

PROVIDER: S-EPMC7383876 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET.

Mecca Adam P AP Chen Ming-Kai MK O'Dell Ryan S RS Naganawa Mika M Toyonaga Takuya T Godek Tyler A TA Harris Joanna E JE Bartlett Hugh H HH Zhao Wenzhen W Nabulsi Nabeel B NB Wyk Brent C Vander BCV Varma Pradeep P Arnsten Amy F T AFT Huang Yiyun Y Carson Richard E RE van Dyck Christopher H CH

Alzheimer's & dementia : the journal of the Alzheimer's Association 20200513 7

<h4>Introduction</h4>Synaptic loss is a robust and consistent pathology in Alzheimer's disease (AD) and the major structural correlate of cognitive impairment. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising biomarker of synaptic density.<h4>Methods</h4>We measured SV2A binding in 34 participants with early AD and 19 cognitively normal (CN) participants using [<sup>11</sup> C]UCB-J PET and a cerebellar reference region for calculat ...[more]

PMID: 32400950

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Project description:The aim of this study was to explore the cerebral distribution of the tau-specific PET tracer [(18)F]THK5317 (also known as (S)-[(18)F]THK5117) retention in different stages of Alzheimer's disease; and study any associations with markers of hypometabolism and amyloid-beta deposition.Thirty-three individuals were enrolled, including nine patients with Alzheimer's disease dementia, thirteen with mild cognitive impairment (MCI), two with non-Alzheimer's disease dementia, and nine healthy controls (five young and four elderly). In a multi-tracer PET design [(18)F]THK5317, [(11)C] Pittsburgh compound B ([(11)C]PIB), and [(18)F]FDG were used to assess tau pathology, amyloid-beta deposition and cerebral glucose metabolism, respectively. The MCI patients were further divided into MCI [(11)C]PIB-positive (n?=?11) and MCI [(11)C]PIB-negative (n?=?2) groups.Test-retest variability for [(18)F]THK5317-PET was very low (1.17-3.81 %), as shown by retesting five patients. The patients with prodromal (MCI [(11)C]PIB-positive) and dementia-stage Alzheimer's disease had significantly higher [(18)F]THK5317 retention than healthy controls (p?=?0.002 and p?=?0.001, respectively) in areas exceeding limbic regions, and their discrimination from this control group (using the area under the curve) was >98 %. Focal negative correlations between [(18)F]THK5317 retention and [(18)F]FDG uptake were observed mainly in the frontal cortex, and focal positive correlations were found between [(18)F]THK5317 and [(11)C]PIB retentions isocortically. One patient with corticobasal degeneration syndrome and one with progressive supranuclear palsy showed no [(11)C]PIB but high [(18)F]THK5317 retentions with a different regional distribution from that in Alzheimer's disease patients.The tau-specific PET tracer [(18)F]THK5317 images in vivo the expected regional distribution of tau pathology. This distribution contrasts with the different patterns of hypometabolism and amyloid-beta deposition.

Dataset Information

In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET.

Publications

In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET.

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