Recently, the research study Associations Between Serum Cholesterol Levels and Cerebral Amyloidosis, published in the journal JAMA Neurology, gained a lot of attention in the press. Somehow it was construed that the study had revealed a direct relationship between cholesterol levels and Alzheimer’s risk. Is that really what the research showed? Let’s take a look.
The study evaluated total cholesterol levels, level of HDL and LDL in a group of 74 elderly individuals. In addition, each of the subjects underwent a special type of brain scan to determine how much β-amyloid their brain contained. β-amyloid was studied because some researchers still believe that there is a relationship between β-amyloid levels and Alzheimer’s risk.
The marker for β-amyloid used in the study is something called PIB. Here is what the authors published:
Higher LDL-C and lower HDL-C levels were both associated with a higher PIB index. No association was found between the total cholesterol level and PIB index. No association was found between statin use and PIB index, and controlling for cholesterol treatment in the statistical models did not alter the basic findings.
Basically, there was a small, increased risk of having higher β-amyloid if the subjects had high LDL or low HDL with no correlation to cholesterol values or statin use.
Does this mean there is a definite connection of low HDL or high LDL to Alzheimer’s disease risk? The answer is clearly no. The hypothesis that somehow β-amyloid is responsible for Alzheimer’s disease was, until recently, popular amongst neuroscientists, especially those involved in drug development. Millions of dollars have been expended in attempts to develop a drug therapy to rid the brain of β-amyloid in hopes of offering up a treatment for Alzheimer’s disease. And each and every trial has failed, with the most recent report in the New England Journal of Medicine showing that a drug, Semagacestat, designed to lower β-amyloid, actually made people more demented and increased the risk for other threatening issues. Here is what the authors of the study concluded:
As compared with placebo, Semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability. Semagacestat was associated with more adverse events, including skin cancers and infections.
In fact, new research in directly challenging the hypothesis that β-amyloid is a player in causing Alzheimer’s disease. As Rudy J. Castellani, Jr., MD, Director of Neuropathology at the University of Maryland recently stated:
Based on my interaction with various neuroscientists and clinicians in the field, the dominant hypothesis — the so-called amyloid cascade … is widely viewed as seriously flawed…Unfortunately, there is a lot of money and associated influence, as well as prestigious names and titles with a personal stake in the ultimate success of treatment efforts modeled after their preferred construct. Alzheimer’s research involves selling ideas as much as (and more in my view) objective pursuit of knowledge. In this respect, the peer review process is a bit of a farce, as it encourages fealty to existing ideas and hampers innovation, in spite of unending lip service paid to the latter… The popular press (major media outlets, many of them) will run articles, with or without schematic representations, along with quotes from esteemed researchers at the world’s top institutions… They speak of (overly simplistic) removal of bad proteins, the exciting results from (hopelessly irrelevant) experimental models, economic burdens to society if something isn’t done, anecdotal accounts of human intervention, etc, etc. All this, which taken together amounts to no more than snake oil in terms of a cure, permeates public thought and pretty soon everyone wants to be vaccinated [against beta amyloid]. Lost in the process is a hypothesis that is deeply flawed and certainly unproven.
His research on this subject has been published in the Journal of Alzheimer’s Disease. The key points are found on the very insightful website The Tangled Neuron – A Layperson Reports on Memory Loss, Alzheimer’s & Dementia, where the idea that β-amyloid may actually be brain–protective is explored, going so far as to suggest that β-amyloid may actually be a brain-protective antioxidant.
Other researchers believe that β-amyloid may actually represent the brain’s response to invading viruses as recently reported in the Huffington Post where I stated:
It turns out that beta-amyloid is an “antimicrobial peptide,” a technical term for a protein that helps get rid of foreign organisms. Indeed, Dr. Ruth Itzhaki from the University of Manchester has published extensively demonstrating compelling evidence of the central role of the herpes simplex virus in Alzheimer’s disease.
So consider that beta-amyloid is increased in the Alzheimer’s not as a cause, but rather as an effect. This protein, the target of so many failed pharmaceutical campaigns, may well be our brain’s desperate response to an invading organism, herpes simplex or who knows what else. So we should reconsider our thought process on what underlies this devastating disease, especially as it relates to the role of beta-amyloid. Remember, the enemy of my enemy is my friend.
It’s so important to provide the full story when media spins research like we saw with this recent publication. The mission is to light the single candle and, while not cursing the darkness, reveal how misguided are the ongoing efforts to castigate and medically remediate parameters that may actually be doing no harm.