Dataset Information

Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [¹¹ C]UCB-J.

ABSTRACT:

Introduction

For 30 years synapse loss has been referred to as the major pathological correlate of cognitive impairment in Alzheimer's disease (AD). However, this statement is based on remarkably few patients studied by autopsy or biopsy. With the recent advent of synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, we have begun to evaluate the consequences of synaptic alterations in vivo.

Methods

We examined the relationship between synaptic density measured by [¹¹ C]UCB-J PET and neuropsychological test performance in 45 participants with early AD.

Results

Global synaptic density showed a significant positive association with global cognition and performance on five individual cognitive domains in participants with early AD. Synaptic density was a stronger predictor of cognitive performance than gray matter volume.

Conclusion

These results confirm neuropathologic studies demonstrating a significant association between synaptic density and cognitive performance, and suggest that this correlation extends to the early stages of AD.

SUBMITTER: Mecca AP

PROVIDER: S-EPMC9381645 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [<sup>11</sup> C]UCB-J.

Mecca Adam P AP O'Dell Ryan S RS Sharp Emily S ES Banks Emmie R ER Bartlett Hugh H HH Zhao Wenzhen W Lipior Sylwia S Diepenbrock Nina G NG Chen Ming-Kai MK Naganawa Mika M Toyonaga Takuya T Nabulsi Nabeel B NB Vander Wyk Brent C BC 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 20220217 12

<h4>Introduction</h4>For 30 years synapse loss has been referred to as the major pathological correlate of cognitive impairment in Alzheimer's disease (AD). However, this statement is based on remarkably few patients studied by autopsy or biopsy. With the recent advent of synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, we have begun to evaluate the consequences of synaptic alterations in vivo.<h4>Methods</h4>We examined the relationship between synaptic densit ...[more]

PMID: 35174954

Similar Datasets

Project description:BackgroundAttempts to associate amyloid-β (Aβ) pathogenesis with synaptic loss in Alzheimer's disease (AD) have thus far been limited to small numbers of postmortem studies. Aβ plaque burden is not well-correlated with indices of clinical severity or neurodegeneration-at least in the dementia stage-as deposition of Aβ reaches a ceiling. In this study, we examined in vivo the association between fibrillar Aβ deposition and synaptic density in early AD using positron emission tomography (PET). We hypothesized that global Aβ deposition would be more strongly inversely associated with hippocampal synaptic density in participants with amnestic mild cognitive impairment (aMCI; a stage of continued Aβ accumulation) compared to those with dementia (a stage of relative Aβ plateau).MethodsWe measured SV2A binding ([11C]UCB-J) and Aβ deposition ([11C]PiB) in 14 participants with aMCI due to AD and 24 participants with mild AD dementia. Distribution volume ratios (DVR) with a cerebellar reference region were calculated for both tracers to investigate the association between global Aβ deposition and SV2A binding in hippocampus. Exploratory analyses examined correlations between both global and regional Aβ deposition and SV2A binding across a broad range of brain regions using both ROI- and surface-based approaches.ResultsWe observed a significant inverse association between global Aβ deposition and hippocampal SV2A binding in participants with aMCI (r = - 0.55, P = 0.04), but not mild dementia (r = 0.05, P = 0.82; difference statistically significant by Fisher z = - 1.80, P = 0.04). Exploratory analyses across other ROIs and whole brain analyses demonstrated no broad or consistent associations between global Aβ deposition and regional SV2A binding in either diagnostic group. ROI-based analyses of the association between regional Aβ deposition and SV2A binding also revealed no consistent pattern but suggested a "paradoxical" positive association between local Aβ deposition and SV2A binding in the hippocampus.ConclusionsOur findings lend support to a model in which fibrillar Aβ is still accumulating in the early stages of clinical disease but approaching a relative plateau, a point at which Aβ may uncouple from neurodegenerative processes including synaptic loss. Future research should investigate the relationship between Aβ deposition and synaptic loss in larger cohorts beginning preclinically and followed longitudinally in conjunction with other biomarkers.

Dataset Information

Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [¹¹ C]UCB-J.

Introduction

Methods

Results

Conclusion

Publications

Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [<sup>11</sup> C]UCB-J.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11 C]UCB-J.

Introduction

Methods

Results

Conclusion

Publications

Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [<sup>11</sup> C]UCB-J.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [¹¹ C]UCB-J.