CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Clinical pathology abstracts editor: Deborah Sesok-Pizzini, MD, MBA, associate professor, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, and medical director, Blood Bank and Transfusion Medicine, Children’s Hospital of Philadelphia.
Variant of TREM2 associated with risk of Alzheimer’s disease
Alzheimer’s disease is the most common form of dementia in the elderly. The disease is characterized by the formation of extracellular amyloid plaques, intracellular neurofibrillary tangles, and loss of neurons, which results in brain atrophy and progressive loss of cognitive function. Variants in the genomic sequence, including APP, PSEN1, and PSEN2, have been described and are associated with the development of Alzheimer’s disease prior to 60 years of age. However, the majority of Alzheimer’s disease is late onset, and the most common variant associated with this is apolipoprotein E (ApoE). The authors conducted a study to search for additional sequence variants associated with Alzheimer’s disease in a patient cohort from Iceland. They performed whole-genome sequencing of samples from 2,261 Icelanders and found 191,777 functional variants, including frameshift, splicing, and stop gain-loss variants. The authors noted that these were the variants most likely to affect protein function. They then imputed these sequence variants into the genomes of patients with Alzheimer’s disease and control participants and searched for an association with Alzheimer’s disease. They also performed replication tests using case-control series from the United States, Norway, Netherlands, and Germany. The authors concluded that they found a rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor on myeloid cells 2 (TREM2), which was found to be a significant risk predictor for Alzheimer’s disease in Iceland (odds ratio, 2.92; 95 percent confidence interval, 2.09–4.09). Interestingly, the study also showed that carriers of the mutation rs75932628-T who were between the ages of 80 and 100 years and who did not have Alzheimer’s disease had poorer cognitive function than noncarriers. The authors hypothesized that the variant TREM2 may impair the inflammatory process, leading to an increased predisposition to Alz-heimer’s disease.
Jonsson T, Stefansson H, Steinberg S, et al. Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med. 2012. doi:10.1056/NEJMoa1211103.
Correspondence: Dr. K. Stefansson at kstefans@decode.is