The APOE extremes study entails Alzheimer’s disease (AD) case-control association analysis using an age extremes sampling approach stratified by APOE genotype, comparing younger onset AD cases against older cognitively normal controls. We queried the National Alzheimer’s Coordinating Center database to select individuals of self-reported European ancestry that lacked sequencing data and matched the following criteria: APOE ε4/ε4 or ε3/ε4 AD cases with age at onset ≤ 65 years, APOE ε4/ε4 controls with age at last assessment ≥ 75 years, or APOE ε3/ε4 controls with age at last assessment ≥ 80 years. DNA samples were provided by the National Cell Repository of Alzheimer’s Disease. Whole genome sequencing was performed at Illumina. PCR-amplified, paired-end Illumina libraries were generated then underwent paired-end sequencing on an Illumina HiSeq 2000.

Alison Goate, DPhil.
Mount Sinai School of Medicine

Gerard Schellenberg, PhD.
University of Pennsylvania

National Institute on Aging U01AG049508 “Modifier Genes that Influence Age at Onset or Protect Against Development of Alzheimer’s Disease” (PI Alison M. Goate).

Genentech (PI Alison M. Goate, Robert R. Graham).

Alzheimer’s Disease Genetics Consortium, U01AG032984 (PI Gerard Schellenberg)

Acknowledgment statement for any data distributed by NIAGADS:

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer's Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

For investigators using NACC Genentech Study data:

We would like to thank study participants, their families, and the sample collectors for their invaluable contributions. This research was supported in part by the National Institute on Aging grant U01AG049508 (PI Alison M. Goate). This research was supported in part by Genentech, Inc. (PI Alison M. Goate, Robert R. Graham).

The NACC database is funded by NIA/NIH Grant U01 AG016976. NACC data are contributed by these NIA-funded ADCs: P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG005131 (PI Douglas Galasko, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG005681 (PI John Morris, MD), P30 AG028377 (Kathleen Welsh-Bohmer, PhD), and P50 AG008671 (PI Henry Paulson, MD, PhD).

Samples from the National Cell Repository for Alzheimer’s Disease (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA), were used in this study. We thank contributors who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible.

The Alzheimer's Disease Genetics Consortium supported the collection of samples used in this study through National Institute on Aging (NIA) grants U01AG032984 and RC2AG036528.

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