Elevated levels of low-density lipoprotein (LDL) cholesterol are associated with early-onset Alzheimer’s disease, according to a study published online in JAMA Neurology.
“The big question is whether there is a causal link between cholesterol levels in the blood and Alzheimer's disease risk,” said lead author Thomas S. Wingo, MD, a neurologist and researcher with the Atlanta Veterans Affairs Medical Center and Emory University, Atlanta, Georgia.
“The existing data have been murky on this point. One interpretation of our current data is that LDL cholesterol does play a causal role. If that is the case, we might need to revise targets for LDL cholesterol to help reduce Alzheimer's risk. Our work now is focused on testing whether there is a causal link.”
Higher cholesterol levels have previously been associated with an increased risk of Alzheimer’s disease later in life. To investigate whether a similar link exists between cholesterol and early-onset Alzheimer’s disease, researchers analyzed plasma samples from 2125 people, 654 of whom had early-onset Alzheimer’s disease.
Study participants with higher LDL levels were more likely to have early-onset Alzheimer’s disease, researchers found, independent of the effects of an APOE gene variant known to be linked with the disease. This suggests LDL cholesterol could be an independent risk factor for early-onset Alzheimer’s disease whether or not the APOE mutation is present.
Higher levels of high-density lipoprotein (HDL) cholesterol were not associated with early-onset Alzheimer’s disease.
The study also found a higher rate of early-onset Alzheimer’s disease in participants with a rare variant of the APOB gene, a known influencer of cholesterol levels.
“Collectively, these novel findings highlight the important role of LDL cholesterol in early-onset Alzheimer’s disease pathogenesis,” Dr. Wingo and colleagues wrote, “and suggest a direct link of APOB variants to Alzheimer’s disease risk.”
Wingo TS, Cutler DJ, Wingo AP, et al. Association of early-onset Alzheimer disease with elevated low-density lipoprotein cholesterol levels and rare genetic coding variants of APOB. JAMA Neurology. 2019 May 28;[Epub ahead of print].