SV2A PET shows hippocampal synaptic loss in cognitively unimpaired APOE ε4/ε4 homozygotes

IF 13 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2024-10-30 DOI:10.1002/alz.14327

Anniina Snellman, Jouni Tuisku, Mikko Koivumäki, Saara Wahlroos, Richard Aarnio, Johan Rajander, Mira Karrasch, Laura L. Ekblad, Juha O. Rinne

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Abstract

INTRODUCTION

We investigated hippocampal synaptic density using synaptic vesicle 2A positron emission tomography (PET), and its association with amyloid beta (Aβ) and cognitive performance in healthy apolipoprotein E (APOE) ε4 carriers.

METHODS

Synaptic density was assessed in 46 individuals (APOE ε4/ε4 n = 14; APOE ε3/ε4 n = 16; APOE ε3/ε3 n = 16) with [¹¹C]UCB-J-PET standardized uptake value ratios (SUVRs), by using the centrum semiovale as a reference region. Differences in hippocampal [¹¹C]UCB-J SUVRs were analyzed with analysis of variance (ANOVA) and linear models. Associations among [¹¹C]UCB-J SUVR, Aβ, hippocampal volume, and cognitive variables were analyzed with Spearman correlation.

RESULTS

Hippocampal synaptic density was different among the APOE groups (P_ANOVA= 0.016): APOE ε4/ε4 carriers had lower [¹¹C]UCB-J SUVRs compared to APOE ε3/ε3 (p = 0.013). Hippocampal synaptic density did not correlate with Consortium to Establish a Registry for Alzheimer's Disease (CERAD) total score (rho = −0.052, p = 0.74), Alzheimer's Prevention Initiative Preclinical Cognitive Composite (APCC) score (rho = 0.17, p = 0.28), or [¹¹C]PiB uptake (rho = −0.10, p = 0.50).

DISCUSSION

Hippocampal synaptic loss emerges early in the AD continuum and is measurable in vivo in cognitively unimpaired high-risk individuals.

Highlights

Synaptic density was studied in vivo in healthy older adults using [¹¹C]UCB-J positron emission tomography.
Apolipoprotein E (APOE) ε4/ε4 carriers had lower hippocampal synaptic density compared to APOE ε3/ε3.
Synaptic density was not associated with cognitive performance in this population.
Hippocampal synaptic alterations occur before clinical symptoms in APOE ε4/ε4 carriers.

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SV2A PET 显示认知功能未受损的 APOE ε4/ε4 同源基因携带者海马突触缺失

我们利用突触泡 2A 正电子发射断层扫描（PET）研究了海马突触密度及其与淀粉样β（Aβ）和健康载脂蛋白 E（APOE）ε4 携带者认知能力的关系。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.