APOE genotype determines cell-type-specific pathological landscape of Alzheimer’s disease

• Published in: Neuron (Cambridge, Mass.) Vol. 113; no. 9; pp. 1380 - 1397.e7
• Main Authors: Li, Zonghua, Martens, Yuka A., Ren, Yingxue, Jin, Yunjung, Sekiya, Hiroaki, Doss, Sydney V., Kouri, Naomi, Castanedes-Casey, Monica, Christensen, Trace A., Miller Nevalainen, Lindsay B., Takegami, Nanaka, Chen, Kai, Liu, Chia-Chen, Soto-Beasley, Alexandra, Boon, Baayla D.C., Labuzan, Sydney A., Ikezu, Tadafumi C., Chen, Yixing, Bartkowiak, Alexander D., Xhafkollari, Gisela, Wetmore, Allison M., Bennett, David A., Reichard, Ross R., Petersen, Ronald C., Kanekiyo, Takahisa, Ross, Owen A., Murray, Melissa E., Dickson, Dennis W., Bu, Guojun, Zhao, Na
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.05.2025
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer’s disease; APOE; Apolipoprotein E2 - genetics; Apolipoprotein E3 - genetics; Apolipoprotein E4 - genetics; Apolipoproteins E - genetics; Female; Genotype; Humans; inflammation; Male; Microglia - metabolism; Microglia - pathology; microglia activation; myelination; Neurons - metabolism; Neurons - pathology; Oligodendroglia - metabolism; Oligodendroglia - pathology; single-nucleus RNA sequencing; Synapses - metabolism; synaptic loss; Temporal Lobe - metabolism; Temporal Lobe - pathology; Alzheimer’s disease; synaptic loss; single-nucleus RNA sequencing; inflammation; myelination; microglia activation; APOE
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2025.02.017

The apolipoprotein E (APOE) gene is the strongest genetic risk modifier for Alzheimer’s disease (AD), with the APOE4 allele increasing risk and APOE2 decreasing it compared with the common APOE3 allele. Using single-nucleus RNA sequencing of the temporal cortex from APOE2 carriers, APOE3 homozygotes...