Gerard Schellenberg and colleagues report a genome-wide association study of late-onset Alzheimer's disease (LOAD), as part of the Alzheimer Disease Genetics Consortium. They identify common variants in MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 associated with LOAD. The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (PM) = 1.7 × 10−9, joint analysis P (PJ) = 1.7 × 10−9; stages 1, 2 and 3, PM = 8.2 × 10−12), CD2AP (rs9349407; stages 1, 2 and 3, PM = 8.6 × 10−9), EPHA1 (rs11767557; stages 1, 2 and 3, PM = 6.0 × 10−10) and CD33 (rs3865444; stages 1, 2 and 3, PM = 1.6 × 10−9). We also replicated previous associations at CR1 (rs6701713; PM = 4.6 × 10−10, PJ = 5.2 × 10−11), CLU (rs1532278; PM = 8.3 × 10−8, PJ = 1.9 × 10−8), BIN1 (rs7561528; PM = 4.0 × 10−14, PJ = 5.2 × 10−14) and PICALM (rs561655; PM = 7.0 × 10−11, PJ = 1.0 × 10−10), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility1,2,3.

Dementia is a serious public health problem with an increasing prevalence because of the aging of the population.¹ Dementia is characterized by global cognitive decline sufficient to affect functioning.² It is a chronic illness with seriously disabling effects for patients, their families, and society.² Mild cognitive impairment (MCI) describes cognitive impairment in elderly persons not of sufficient severity to qualify for a diagnosis of dementia.³ Individuals with MCI have complaints of impairment in memory or other areas of cognitive functioning usually noticeable to those around them. In addition, their performance on memory and cognitive tests is below that expected for their age and education. However, their day-to-day functioning is generally preserved. Several operational definitions for MCI have been proposed.^3,4 Mild cognitive impairment is a chronic condition and may be a precursor to Alzheimer-type dementia.⁴ Mild cognitive impairment is often worrisome to patients and families, and is increasingly a presenting complaint for care.