Low-density lipoprotein (LDL) cholesterol is associated with the probability of developing early-onset Alzheimer disease (EOAD), according to a study published online May 28 in JAMA Neurology.

Thomas S. Wingo, M.D., from the Atlanta Veterans Affairs Medical Center in Decatur, Georgia, and colleagues measured plasma cholesterol levels in 267 samples. The correlation between cholesterol and EOAD was examined in a case series. APOB (which codes for the major protein of LDL cholesterol), APP, PSEN1, and PSEN2 were sequenced from 2,125 EOAD cases and controls to determine the underlying genetic causes.

The researchers found that APOE ε4 explained 10.1 percent of the variance in EOAD. In 267 frozen samples, EOAD cases had higher levels than controls of total cholesterol, LDL cholesterol, and apolipoprotein B (mean difference, 21.9 mg/dL, 22.0 mg/dL, and 12.0 mg/dL, respectively) after controlling for APOE ε4. About 3 percent of EOAD cases harbored known mutations causing AD. In 2,066 samples, gene-based rare variant burden testing showed that rare APOB coding variants were significantly more abundant in EOAD cases than controls (effect size, 0.20) after adjustment for confounding variables.

"The big question is whether there is a causal link between cholesterol levels in the blood and Alzheimer's disease risk," Wingo said in a statement. "The existing data have been murky on this point. One interpretation of our current data is that LDL cholesterol does play a causal role."

Several authors disclosed financial ties to the pharmaceutical industry.

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