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海马体淀粉样β负担与神经纤维缠结空间分布的关系。

The relationship between hippocampal amyloid beta burden and spatial distribution of neurofibrillary degeneration.

机构信息

Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

出版信息

Alzheimers Dement. 2023 Jul;19(7):3158-3170. doi: 10.1002/alz.12966. Epub 2023 Feb 4.

Abstract

INTRODUCTION

Neurofibrillary degeneration in Alzheimer's disease (AD) typically involves the entorhinal cortex and CA1 subregion of the hippocampus early in the disease process, whereas in primary age-related tauopathy (PART), there is an early selective vulnerability of the CA2 subregion.

METHODS

Image analysis-based quantitative pixel assessments were used to objectively evaluate amyloid beta (Aβ) burden in the medial temporal lobe in relation to the distribution of hyperphosphorylated-tau (p-tau) in 142 cases of PART and AD.

RESULTS

Entorhinal, CA1, CA3, and CA4 p-tau deposition levels are significantly correlated with Aβ burden, while CA2 p-tau is not. Furthermore, the CA2/CA1 p-tau ratio is inversely correlated with Aβ burden and distribution. In addition, cognitive impairment is correlated with overall p-tau burden.

DISCUSSION

These data indicate that the presence and extent of medial temporal lobe Aβ may determine the distribution and spread of neurofibrillary degeneration. The resulting p-tau distribution patterns may discriminate between PART and AD.

HIGHLIGHTS

Subregional hyperphosphorylated-tau (p-tau) distribution is influenced by hippocampal amyloid beta burden. Higher CA2/CA1 p-tau ratio is predictive of primary age-related tauopathy-like neuropathology. Cognitive function is correlated with the overall hippocampal p-tau burden.

摘要

简介

阿尔茨海默病(AD)中的神经纤维缠结变性通常在疾病早期涉及到内嗅皮层和海马体的 CA1 亚区,而在原发性年龄相关性 tau 病(PART)中,CA2 亚区则存在早期选择性易损性。

方法

采用基于图像分析的定量像素评估方法,客观评估 142 例 PART 和 AD 患者内侧颞叶中淀粉样β(Aβ)负担与磷酸化-tau(p-tau)分布的关系。

结果

内嗅皮层、CA1、CA3 和 CA4 的 p-tau 沉积水平与 Aβ 负担显著相关,而 CA2 的 p-tau 则不相关。此外,CA2/CA1 的 p-tau 比值与 Aβ 负担和分布呈负相关。此外,认知障碍与总 p-tau 负担相关。

讨论

这些数据表明,内侧颞叶 Aβ 的存在和程度可能决定了神经纤维缠结变性的分布和传播。由此产生的 p-tau 分布模式可区分 PART 和 AD。

重点

海马体淀粉样β负担影响亚区磷酸化-tau(p-tau)的分布。较高的 CA2/CA1 p-tau 比值预示着原发性年龄相关性 tau 病样神经病理学。认知功能与海马体总 p-tau 负担相关。

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