Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report

• Published in: Nature medicine Vol. 25; no. 11; pp. 1680 - 1683
• Main Authors: Arboleda-Velasquez, Joseph F, Lopera, Francisco, O'Hare, Michael, Delgado-Tirado, Santiago, Marino, Claudia, Chmielewska, Natalia, Saez-Torres, Kahira L, Amarnani, Dhanesh, Schultz, Aaron P, Sperling, Reisa A, Leyton-Cifuentes, David, Chen, Kewei, Baena, Ana, Aguillon, David, Rios-Romenets, Silvia, Giraldo, Margarita, Guzmán-Vélez, Edmarie, Norton, Daniel J, Pardilla-Delgado, Enmanuelle, Artola, Arabiye, Sanchez, Justin S, Acosta-Uribe, Juliana, Lalli, Matthew, Kosik, Kenneth S, Huentelman, Matthew J, Zetterberg, Henrik, Blennow, Kaj, Reiman, Rebecca A, Luo, Ji, Chen, Yinghua, Thiyyagura, Pradeep, Su, Yi, Jun, Gyungah R, Naymik, Marcus, Gai, Xiaowu, Bootwalla, Moiz, Ji, Jianling, Shen, Lishuang, Miller, John B, Kim, Leo A, Tariot, Pierre N, Johnson, Keith A, Reiman, Eric M, Quiroz, Yakeel T
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.11.2019
• Subjects: Age; Aged; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid - genetics; Amyloid - metabolism; Apolipoprotein E; Apolipoprotein E2 - genetics; Apolipoprotein E3 - genetics; Brain - diagnostic imaging; Brain - metabolism; Brain - pathology; Brain research; Care and treatment; Case reports; Cognitive ability; Cognitive Dysfunction - genetics; Cognitive Dysfunction - pathology; Dementia; Drug resistance; Female; Gene mutations; Homozygote; Hospitals; Humans; Laboratories; Male; Medical imaging; Medical research; Medical schools; Medical treatment; Medicine; Medicine, Experimental; Mutation; Mutation - genetics; Neurochemistry; Neurodegeneration; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - pathology; Neurology; Neurosciences; Neurovetenskaper; Pathogenesis; Pathology; Pedigree; Presenilin 1; Presenilin-1 - genetics; Proteins; Research centers; Tau protein
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/s41591-019-0611-3

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.