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tau蛋白沉积在唐氏综合征早期认知衰退中的作用。

Role of tau deposition in early cognitive decline in Down syndrome.

作者信息

Hartley Sigan L, Handen Benjamin L, Tudorascu Dana, Lee Laise, Cohen Annie, Piro-Gambetti Brianna, Zammit Matthew, Klunk William, Laymon Charles, Zaman Shahid, Ances Beau M, Sabbagh Marwan, Christian Bradley T

机构信息

Waisman Center University of Wisconsin-Madison Madison Wisconsin USA.

School of Human Ecology University of Wisconsin-Madison Madison Wisconsin USA.

出版信息

Alzheimers Dement (Amst). 2022 Apr 1;14(1):e12256. doi: 10.1002/dad2.12256. eCollection 2022.

DOI:10.1002/dad2.12256
PMID:35386473
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8976157/
Abstract

INTRODUCTION

Drawing on the amyloid/tau/neurodegeneration (AT[N]) model, the study examined whether the tau positron emission tomography (PET) biomarker [F]AV-1451 was associated with episodic memory problems beyond what was predicted by the amyloid beta (Aβ) PET in Down syndrome (DS).

METHODS

Data from 123 non-demented adults with DS ( = 47 years, standard deviation = 6.34) were analyzed. The Cued Recall Test assessed episodic memory. Tau PET standardized update value ratio (SUVR) was assessed across Braak regions as continuous and binary (high tau [T] vs. low tau [T]) variable. Global PET Aβ SUVR was assessed as binary variable (Aβ- vs. Aβ+).

RESULTS

In models adjusting for controls, tau SUVR was negatively associated with episodic memory performance in the Aβ+ but not Aβ- group. The Aβ+/T group evidenced significantly worse episodic memory than the Aβ+/T group.

DISCUSSION

Similar to late-onset and autosomal dominant Alzheimer's disease (AD), high tau was an indicator of early prodromal AD in DS.

摘要

引言

基于淀粉样蛋白/ tau蛋白/神经退行性变(AT[N])模型,本研究探讨了tau正电子发射断层扫描(PET)生物标志物[F]AV-1451是否与唐氏综合征(DS)中超出淀粉样β蛋白(Aβ)PET预测范围的情景记忆问题相关。

方法

分析了123名非痴呆的DS成年人(年龄=47岁,标准差=6.34)的数据。线索回忆测试评估情景记忆。tau PET标准化摄取值比率(SUVR)在Braak区域作为连续变量和二元变量(高tau [T]与低tau [T])进行评估。整体PET Aβ SUVR作为二元变量(Aβ-与Aβ+)进行评估。

结果

在对对照进行调整的模型中,tau SUVR在Aβ+组而非Aβ-组中与情景记忆表现呈负相关。Aβ+/T组的情景记忆明显比Aβ+/T组差。

讨论

与晚发性和常染色体显性阿尔茨海默病(AD)相似,高tau是DS中早期前驱AD的一个指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd1e/8976157/109e93d8e0ca/DAD2-14-e12256-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd1e/8976157/109e93d8e0ca/DAD2-14-e12256-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd1e/8976157/109e93d8e0ca/DAD2-14-e12256-g001.jpg

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Antisense oligonucleotides directed against App and Rab5 normalized endosomal Rab activity and reversed DS-AD-linked degenerative phenotypes in the Dp16 mouse model of Down syndrome.针对App和Rab5的反义寡核苷酸使内体Rab活性正常化,并逆转了唐氏综合征Dp16小鼠模型中与DS-AD相关的退化表型。
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