cholesterol

Cholesterol & dementia risk

  • A large study found that higher levels of LDL (the "bad" cholesterol) were linked to a higher risk of early-onset Alzheimer's. There was no link between HDL levels and early-onset risk.
  • A long-running study of middle-aged women found that low levels of HDL cholesterol were associated with more vascular brain damage in later life.

High LDL linked to early-onset Alzheimer's

Elevated cholesterol levels have been linked to increased risk of Alzheimer's later in life, and APOE4 is known to raise levels of circulating cholesterol, particularly low-density lipoprotein (LDL) ("bad cholesterol"). A new study has investigated whether LDL is also linked to early-onset Alzheimer's.

The study involved genetically testing 2,125 people, 654 of whom had early-onset Alzheimer's, and testing for cholesterol in a subset of 267 participants. It found that APOE4 explained about 10% of early-onset Alzheimer's, which is similar to estimates in late-onset Alzheimer's disease. About 3% of early-onset Alzheimer's cases had at least one of the known early-onset Alzheimer's risk factors (APP, PSEN1, PSEN2).

Those with elevated LDL levels were more likely to have early-onset Alzheimer's disease, compared with patients with lower cholesterol levels. This was true even after the researchers controlled for APOE genotype.

There was no link between HDL (high-density lipoprotein) cholesterol levels and early-onset Alzheimer's, and only a very slight association between the disease and triglyceride levels.

The researchers also found a new possible genetic risk factor for early-onset Alzheimer's disease. Early-onset Alzheimer's cases were higher in participants with a rare variant of a gene called APOB. This gene encodes a protein that is involved in the metabolism of lipids, or fats, including cholesterol.

https://www.eurekalert.org/pub_releases/2019-05/varc-hll052419.php

Good cholesterol may cut women’s dementia risk

A long-running study found that women who had normal levels of the “good” cholesterol, HDL, in 1992 had less white matter damage in their brain two decades later.

The data come from 135 participants in the long-running Women's Healthy Ageing Project. The study found that a higher cardiovascular risk score in midlife was associated with a greater degree of white matter hyperintensity lesions 20 years later, but, intriguingly, that this was predominantly driven by HDL cholesterol level, after controlling for age, education, and APOEe4 status.

https://www.futurity.org/good-cholesterol-women-brains-dementia-1899132/

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Cholesterol genes link risk of heart disease & Alzheimer’s

  • A very large genetic study provides evidence that cardiovascular disease risk and Alzheimer's risk are related because of one shared element: genes involved in cholesterol and lipid metabolism.

The APOE gene, the strongest genetic risk factor for Alzheimer’s disease, is known to be involved in cholesterol and lipid metabolism. Now the largest ever genetic study of Alzheimer’s disease, using DNA from more than 1.5 million people, has identified 90 points across the genome that were associated with an increased risk of both cardiovascular disease and Alzheimer’s disease.

The study focused on specific risk factors for heart disease (e.g., high BMI, type 2 diabetes, high cholesterol) to see if any were genetically related to Alzheimer’s risk. It was found that only those genes involved in lipid metabolism also related to Alzheimer's risk.

Six of the 90 regions had very strong effects on Alzheimer’s and heightened blood lipid levels, including several points within the CELF1/MTCH2/SPI1 region on chromosome 11 that was previously linked to the immune system.

The same genetic risk factors were also more common in people with a family history of Alzheimer’s, even though they had not themselves developed dementia or MCI.

The findings suggest that cardiovascular and Alzheimer's risk co-occur because of a shared genetic basis.

They also suggest a therapeutic target — namely, pathways involved in lipid metabolism.

https://www.futurity.org/alzheimers-disease-heart-disease-cholesterol-1913312-2/

https://www.eurekalert.org/pub_releases/2018-11/wuso-cda111118.php

Reference: 

Broce I, Karch C, Desikan R, et al. Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer's disease. Acta Neuropathologica, published online Nov. 9, 2018.

 

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