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Dec 30, 2013

Cholesterol Levels in Blood Linked to Amyloid Deposits in Brain

  • Although nearly all cholesterol in the central nervous system is locally synthesized, peripheral cholesterol is suspected of playing a role in cerebral amyloid deposition and contributing to Alzheimer’s disease (AD). Several lines of evidence point to serum cholesterol’s culpability. First, epidemiological studies have found parallels between atherogenic risk factors for cardiac disease and clinically diagnosed AD. Second, observational studies indicate that statin use is associated with reduced odds of AD. Third, genetic studies have shown that a genetic allele for APOE, the primary transporter of cholesterol in the brain, is associated with earlier and higher deposition of amyloid.

    Following up on these clues, scientists from University of California, Davis (UC-Davis), the University of California, Berkeley (UC-Berkeley), and the University of Southern California investigated whether there is an in vivo association between serum lipids and cerebral amyloid deposition. They found that elevated cerebral amyloid level was associated with cholesterol fractions in a pattern analogous to that found in coronary artery disease.

    This finding was reported December 30 in JAMA Neurology, in a paper entitled “Associations between Serum Cholesterol Levels and Cerebral Amyloidosis.” The paper described how the scientists evaluated 74 diverse male and female individuals 70 years and older who were recruited from California stroke clinics, support groups, senior facilities, and the UC Davis Alzheimer’s Disease Center. The study’s participants included three individuals with mild dementia, 33 who were cognitively normal, and 38 who had mild cognitive impairment.

    The participants’ amyloid levels were obtained using a tracer that binds with amyloid plaques and imaging their brains using PET scans. Higher fasting levels of LDL and lower levels of HDL both were associated with greater brain amyloid—a first-time finding linking cholesterol fractions in the blood and amyloid deposition in the brain.

    Charles DeCarli, director of the Alzheimer’s Disease Center and an author of the study, said it is a wake-up call that, just as people can influence their late-life brain health by limiting vascular brain injury through controlling their blood pressure, the same is true of getting a handle on their serum cholesterol levels.

    “If you have an LDL above 100 or an HDL that is less than 40, even if you’re taking a statin drug, you want to make sure that you are getting those numbers into alignment,” DeCarli said. “You have to get the HDL up and the LDL down.”

    Recent guidelines devised by institutions dedicated to cardiac health have suggested abandoning guidelines for LDL targets. This suggestion may be an instance in which the adage that “what’s good for the heart is good for the brain” does not apply, said Bruce Reed, lead study author and associate director of the Alzheimer’s Disease Center.

    Besides raising the possibility that people receiving cholesterol treatment should continue it regardless of their cardiac status, if they are developing memory loss, the study “also suggests a method of lowering amyloid levels in people who are middle aged, when such build-up is just starting,” added Dr. Reed. “If modifying cholesterol levels in the brain early in life turns out to reduce amyloid deposits late in life, we could potentially make a significant difference in reducing the prevalence of Alzheimer's, a goal of an enormous amount of research and drug development effort.”

    Although the researchers did not study the mechanism for how cholesterol promotes amyloid deposits, they did note that such considerations “must account for the fact that essentially all central nervous system cholesterol is locally synthesized and that there is minimal exchange of HDL-C particles and essentially no exchange of LDL-C and very low density lipoprotein cholesterol-C particles across the intact blood-brain barrier.”

    Serum cholesterol levels, speculated the authors, may be related to or interact with chemical species that can both efficiently traverse the blood-brain barrier and also influence amyloidosis. Alternatively, “systemic hyperlipidemia may damage the blood-brain barrier via inflammatory and other mechanisms, with consequent leakage of serum cholesterol, inflammatory cytokines, and other amyloidogenic factors.”



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