Genetic Markers Predict Alzheimer's Disease

A buildup of certain proteins in the brain and spinal fluid has an increased likelihood of people developing Alzheimer's disease.

Mutations identified in certain genetic regions influence the levels of these protein accumulations and this may help identify people most at risk of developing Alzheimer's disease well before they show signs of cognitive decline.

A group of scientists collaborating with those at Washington University School of Medicine (St. Louis, MO, USA) measured the proteins tau, ptau, and Aβ42 in cerebrospinal fluid (CSF) in 1,269 individuals. The mean age at enrollment was 78.5 years and 30.9% were male. At the last evaluation, 24.9% met clinical diagnostic criteria for AD and 21.8% had mild cognitive impairment. The samples were genotyped using Illumina chips (San Diego, CA, USA).

A genetic region identified by the group includes the Alzheimer's disease gene triggering receptor expressed on myeloid cells 2 (TREM2), which encodes a cellular receptor and other genes in TREM2's family, including Trem-like transcript 1 protein (TREML2). Alison Goate, PhD, of the Washington University School of Medical School, said, "Tau is an important biomarker of neurodegeneration in Alzheimer's disease, present as insoluble aggregates in the brain and as soluble protein in the cerebrospinal fluid. We have identified several genes that influence the levels of soluble tau in the cerebrospinal fluid, and we show that one of these genes also influences risk for Alzheimer's disease, rate of cognitive decline in Alzheimer's disease, and density of tangle pathology in the brain."

Carlos Cruchaga, PhD, the first author of the study said, "Interestingly, although these genes are similar, the associations of TREM2 and TREML2 with cerebrospinal fluid tau levels were in the opposite direction, one associated with risk for Alzheimer's disease and the other protective.” The authors concluded that using a genome-wide association study they were able to identify the risk variants for Alzheimer’s disease by measuring the levels of tau in the CSF. The study was published on April 4, 2013, in the journal Neuron.

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