Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report

We identified a PSEN1 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. She had two copies of the APOE3 Christchurch (R136S) mutation, unu...

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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	01.11.2019
Online Access	Get full text
ISSN	1078-8956 1546-170X
DOI	10.1038/s41591-019-0611-3

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Summary:	We identified a PSEN1 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. She had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid, and limited tau/tangle and neurodegenerative measurements. Our findings have implications for APOE’s role in the pathogenesis, treatment, and prevention of Alzheimer’s disease.
Bibliography:	Author contribution Drs. Quiroz and Reiman are co-senior authors. J.F.A.-V., E.M.R., F.L., and Y.T.Q. initiated this work, supervised conduction of the study, and drafted the manuscript. A.B., S.R.-R., D.A., M.G., E.G.-V., D.N., E.P.-D., A.A., L.A.K., and J.B.M., collected and analyzed phenotypic data. M.J.H., M.N., R.A.R., G.R.J., K.S.K., J.A.-U., M.L., X.G, M.B., J.J., K.L.S.-T., L.S., and S.D.-T. collected and analyzed genetic data. N.C. and D.L.-C. conducted and analyzed molecular and genetic studies. K.C., Y.C., P.N.T., J.L., Y.S., P.T., R.A.S, A.P.S., K.A.J., and J.S.S. analyzed and interpreted imaging data, M.O. and C.M. contributed to the biochemistry experiments, data analysis, and to finalize the manuscript. H.Z. and K.B. conducted and analyzed blood biomarker data. Drs. Arboleda-Velasquez, Lopera and O’Hare contributed equally to this article.
ISSN:	1078-8956 1546-170X
DOI:	10.1038/s41591-019-0611-3