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Infection01:20

Infection

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When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
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Urinary Tract Infection II: Pathophysiology

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The pathophysiology of urinary tract infections (UTIs) encompasses several progressive stages, beginning with bacterial colonization and culminating in potential systemic complications if untreated. UTIs are primarily initiated by bacteria, such as Escherichia coli, which often originate from the gastrointestinal tract and migrate to the urinary system through the periurethral area. This migration can occur via several routes, including improper hygiene practices, sexual activity, or...
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Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
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The pathophysiology of pneumonia involves the following steps:
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Stages of Infection01:26

Stages of Infection

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Stages of infection describe what happens to a susceptible host once a pathogen invades the human body. The stages of infection are incubation, prodromal, illness, stage of decline, and convalescence. The incubation stage is the period from exposure to a pathogen until symptoms start. The infected person is unaware of impending illness as the pathogens grow and multiply within the body. The duration may vary depending on the type of infection. The incubation period of measles averages ten to...
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Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

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The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
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Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
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基礎科学と病態生理

Arash Salahinejad1,2,3, Amr Eed1,2,3, Mohammad H Alipour1

  • 1University of Western Ontario, London, ON, Canada.

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|December 28, 2025
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まとめ
この要約は機械生成です。

早期のレカネマブ治療はAPOE4マウスのアルツハイマー病病理を軽減したが、認知機能低下を防ぐことはできず、微小出血を増加させる可能性があった。この研究は、アミロイド標的療法を受けるAPOE4キャリアのリスクを強調するものである。

キーワード:
レカネマブアルツハイマー病APOE4マウスモデルアミロイド病理認知機能微小出血モノクローナル抗体療法

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科学分野:

  • 神経科学; 遺伝学; 薬理学

背景:

  • アルツハイマー病（AD）は認知症の主な原因であり、APOE4キャリアに不釣り合いに影響を与える。; APOE4キャリアは、モノクローナル抗体（mAb）治療において、アミロイドβ（Aβ）蓄積の加速およびアミロイド関連画像異常（ARIA）のリスク増加を示す。; Aβプロトフィブリルを標的とするmAbであるレカネマブは、アミロイドプラークを減少させるが、APOE4キャリアのリスク増大を伴う。

研究 の 目的:

  • 早期レカネマブ（mAb158）治療が、APOE4ヒト化アルツハイマー病マウスモデルにおける微小出血および認知機能低下を軽減できるかどうかを調査すること。; APOE4関連の遺伝的リスクの文脈で、アミロイド病理および脳萎縮に対するmAb158の影響を評価すること。; ADにおけるmAb療法の安全性と有効性を評価するための前臨床プラットフォームを確立すること。

主な方法:

  • ヒト化APP、Tau、およびAPOE3/APOE4遺伝子を有する高度なアルツハイマー病マウスモデルを利用した。; 3ヶ月齢から開始して、hApp^NL-F-hMAPT-APOE4およびhApp^NL-F-hMAPT-APOE3マウスに毎週マウスレカネマブ（mAb158）またはビヒクルを26週間投与した。; 連続遂行テスト（CPT）を用いて認知機能を評価し、顕微鏡検査および生化学的アッセイにより、アミロイド病理、微小出血、およびAβレベルについて脳組織を分析した。

主要な成果:

  • hApp^NL-F-hMAPT-APOE4マウスでは、hApp^NL-F-hMAPT-APOE3マウスと比較して有意なアミロイド蓄積が観察された。; mAb158治療は、15ヶ月齢のhApp^NL-F-hMAPT-APOE4マウスにおける不溶性Aβ蓄積を著しく減少させた。; APOE4マウスは、mAb158治療の有無にかかわらず6ヶ月齢から認知機能低下（CPT）を示し、予備データではmAb158が微小出血を引き起こす可能性が示唆された。

結論:

  • 早期のmAb158治療は、APOE4ヒト化マウスにおいてアルツハイマー病病理を効果的に減少させるが、不注意の低下を防ぐことはできない。; この治療は、脆弱なAPOE4遺伝子型における微小出血のリスクを高める可能性がある。; 本研究は、アルツハイマー病に対するモノクローナル抗体治療の安全性と有効性を予測するための有用な前臨床プラットフォームを示す。