作者
Laura Fernandez Garcia‐Agudo, Zechuan Shi, Ian F Smith, Enikö A Kramár, Katelynn Tran, Shimako Kawauchi, Shuling Wang, Sherilyn Collins, Amber Walker, Kai‐Xuan Shi, Jonathan Neumann, Heidi Yahan Liang, Celia Da Cunha, Giedre Milinkeviciute, Samuel Morabito, Emily Miyoshi, Narges Rezaie, Angela Gomez‐Arboledas, Adrian Mendoza Arvilla, Daryan Iman Ghaemi, Andrea J Tenner, Frank M LaFerla, Marcelo A Wood, Ali Mortazavi, Vivek Swarup, Grant R MacGregor, Kim N Green
发表日期
2024/4
期刊
Alzheimer's & Dementia
卷号
20
期号
4
页码范围
2922-2942
简介
INTRODUCTION
The BIN1 coding variant rs138047593 (K358R) is linked to Late‐Onset Alzheimer's Disease (LOAD) via targeted exome sequencing.
METHODS
To elucidate the functional consequences of this rare coding variant on brain amyloidosis and neuroinflammation, we generated BIN1K358R knock‐in mice using CRISPR/Cas9 technology. These mice were subsequently bred with 5xFAD transgenic mice, which serve as a model for Alzheimer's pathology.
RESULTS
The presence of the BIN1K358R variant leads to increased cerebral amyloid deposition, with a dampened response of astrocytes and oligodendrocytes, but not microglia, at both the cellular and transcriptional levels. This correlates with decreased neurofilament light chain in both plasma and brain tissue. Synaptic densities are significantly increased in both wild‐type and 5xFAD backgrounds homozygous for the BIN1K358R variant …
学术搜索中的文章
LF Garcia‐Agudo, Z Shi, IF Smith, EA Kramár, K Tran… - Alzheimer's & Dementia, 2024