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在患有和未患有阿尔茨海默病病理的认知受损和未受损的老年人中，研究突触密度与神经纤维缠结tau蛋白之间的关联。

Examining the association between synaptic density and neurofibrillary tau among cognitively impaired and unimpaired older adults with and without Alzheimer's disease pathology.

作者信息

DiFilippo Alexandra H, Jonaitis Erin M, Ennis Gilda E, McVea Andrew K, McLachlan Max, Bettcher Brecca, Schulz Nicholas, Pasquesi Mary-Elizabeth, Davenport-Sis Nancy J, Thor Yer, Grover Ethan, Chin Nathaniel, Barnhart Todd E, Asthana Sanjay, Betthauser Tobey J, Engle Jonathan W, Johnson Sterling C, Bendlin Barbara B, Christian Bradley T

机构信息

University of Wisconsin-Madison Waisman Center, Madison, Wisconsin, USA.

University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA.

出版信息

Alzheimers Dement. 2025 Jun;21(6):e70321. doi: 10.1002/alz.70321.

DOI:10.1002/alz.70321
PMID:40465636
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12136093/
Abstract

INTRODUCTION

Synapse loss is a key driver of cognitive decline in Alzheimer's disease (AD), yet its direct relationship with neurofibrillary tau tangle (NFT) burden remains unclear. This study leveraged positron emission tomography (PET) imaging to investigate the link between NFT accumulation and synaptic density in older adults with and without AD pathology.

METHODS

Older adults (N = 94) underwent PET imaging to quantify synaptic density ([C]UCB-J distribution volume ratio [DVR]), Aβ plaque burden ([C]PiB DVR), and NFT burden ([F]MK-6240 standardized uptake value ratio). Analyses focused on NFT-synaptic density correlations in the hippocampus (Hp) and entorhinal cortex (ERC), with additional subgroup analyses based on cognitive and Aβ status.

RESULTS

Hp NFT burden strongly correlated with synaptic density, while the ERC showed weaker effects. Subgroup analyses found robust Hp associations in unimpaired AD participants.

CONCLUSION

Hippocampal synaptic density is highly vulnerable to early NFT accumulation. SV2A PET imaging enables early detection of synaptic loss and may also identify resilience to AD pathology.

HIGHLIGHTS

Hippocampal synaptic density is similar in controls and unimpaired biologic AD. Hp synaptic density particularly vulnerable to Hp, ERC NFT burden. NFT-synaptic density relationship may vary between unimpaired and impaired biologic AD.

摘要

引言

突触丧失是阿尔茨海默病（AD）认知衰退的关键驱动因素，但其与神经纤维缠结（NFT）负担的直接关系仍不清楚。本研究利用正电子发射断层扫描（PET）成像来探究有无AD病理特征的老年人中NFT积累与突触密度之间的联系。

方法

老年人（N = 94）接受PET成像，以量化突触密度（[C]UCB-J分布容积比[DVR]）、Aβ斑块负担（[C]PiB DVR）和NFT负担（[F]MK-6240标准化摄取值比）。分析重点关注海马体（Hp）和内嗅皮质（ERC）中NFT与突触密度的相关性，并基于认知和Aβ状态进行额外的亚组分析。

结果

Hp的NFT负担与突触密度密切相关，而ERC的影响较弱。亚组分析发现，在未受损的AD参与者中，Hp存在显著关联。

结论

海马体突触密度极易受到早期NFT积累的影响。SV2A PET成像能够早期检测突触丧失，还可能识别对AD病理特征的抵抗力。

要点

对照组和未受损的生物学AD患者的海马体突触密度相似。Hp突触密度特别容易受到Hp、ERC的NFT负担影响。NFT与突触密度的关系在未受损和受损的生物学AD之间可能有所不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7db/12136093/1482177a3700/ALZ-21-e70321-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7db/12136093/c30c1899515a/ALZ-21-e70321-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7db/12136093/607a282bbcde/ALZ-21-e70321-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7db/12136093/1482177a3700/ALZ-21-e70321-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7db/12136093/c30c1899515a/ALZ-21-e70321-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7db/12136093/607a282bbcde/ALZ-21-e70321-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7db/12136093/1482177a3700/ALZ-21-e70321-g005.jpg

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