Why Has It Been So Hard to Fight Alzheimer’s?

Dr. Sears' Blog - Why Has It Been So Hard to Fight Alzheimer’s?

Recently, the National Center for Health Statistics announced that death rates in America are increasing for the first time in a decade. The biggest increase in deaths was 15% from Alzheimer’s disease.  Find out the real cause of Alzheimer’s disease and what you can do to prevent it using the Zone.

Our “war” on cancer seems like a victory compared to our pathetic results combating Alzheimer’s. In fact, both “wars” are going nowhere since we often concentrate on defending old theories instead of thinking outside the box. This is especially true in Alzheimer’s where the prevailing theory has been that amyloid plaques, which are clusters of proteins that develop between the nerve cells of the brain, cause Alzheimer’s disease. But what if that theory is wrong? Then billions of dollars in research and equal amounts in drug development studies may have been wasted.

Challenging the Theories on the Cause of Alzheimer’s

What is known about Alzheimer’s disease is that it’s associated with aging, inflammation, and the ApoE4 genotype which is a risk factor for developing late onset Alzheimer’s. Meanwhile, the amyloid plaque hypothesis remains popular, even though clinical data that suggests the causal relationship of amyloid plaques with the loss of mental cognition is not that strong 1-3.

New evidence suggests that amyloid plaque formation may be initially a protection mechanism to prevent microbial invasion in the brain 4. Unlike the rest of the organs in the body where white cells in the blood are transformed into killer cells (neutrophils and macrophages) that can enter the infected area to destroy microbial invasion, the brain is relatively isolated by the blood-brain barrier (BBB). Therefore, the brain relies on Plan B: the formation of a sticky cage built of beta amyloid proteins to trap the microbe so it eventually dies. The cage that is left behind is the amyloid plaque. This hypothesis is in line with new research that shows the BBB is leakier in Alzheimer’s patients than in age-matched normal subjects 5.

Inflammation May Be the Real Cause of Alzheimer’s

So where does inflammation and ApoE4 enter this picture? Inflammation must balance with resolution to maintain wellness.

Evidence supports that a faulty resolution response in Alzheimer’s is caused by a lack of resolution6 which is usually a consequence of inadequate levels of omega-3 fatty acids to produce the hormones known as resolvins. This ties in nicely with the ApoE connection. This particular protein controls the flow of omega-3 fatty acids into the brain. Those individuals who have an ApoE4 mutation, meaning that the resolution of inflammation caused by the debris of the dying microbe trapped within the amyloid plaque cage in the brain is compromised7, have microbial debris that remains a constant source of inflammation that eventually causes the death of brain cells.

How to Resolve Inflammation in the Brain

So what can you do? It turns out a lot. First, reduce the leakiness of the BBB8. Leakiness is usually caused by increased production of leukotrienes derived from arachidonic acid (AA). The best way to reduce arachidonic acid is to follow a strict Zone Diet.

Second, increase the levels of omega-3 fatty acids in your blood so more omega-3s can get into the brain to generate resolvins. If you happen to have the ApoE4 mutation, then you should take even more omega-3 fatty acids which include EPA and DHA from fish oil9.

Not surprisingly, the AA/EPA ratio is higher in Alzheimer’s patients than in age-matched normal subjects10. Zone Labs offers a Cellular Inflammation Test Kit that you can use to find your AA/EPA ratio. If you want to be even more preventative, then add high-doses of polyphenols to your diet, as they demonstrate an increase in cognitive improvement, most likely by reducing insulin resistance in the brain11.

The best prevention for inflammation in the brain is a comprehensive anti-inflammatory nutrition program which includes calorie-restriction, without hunger or fatigue, coupled with high-doses of omega-3 fatty acids and polyphenols. The diet has to be adequate in protein, moderate in carbohydrate (but rich in fermentable fiber), and low in fat (especially omega-6 and saturated fats) which is built into the Zone’s program.

If people don’t start following an anti-inflammatory diet, Alzheimer’s rates will continue to rise and tax dollars will continue to skyrocket, funding research in the wrong area of focus — preventing the formation of amyloid plaques.

Research has proven that amyloid plaques can actually be useful. In animal models, researchers were able to prevent the formation of amyloid plaques through genetic engineering, but the animals quickly died of infection when microbes entered their brains4. It is the resolution of inflammation left by amyloid plaques, and not the plaques themselves, that is the real danger in terms of Alzheimer’s.


  1. Bennett DA et al. “Neuropathology of older persons without cognitive impairment from two community-related studies.” Neurol 66:1837 (2006).
  2. Morris JC et al. “ApoE predicts amyloid-beta, but not tau Alzheimer pathology in cognitively normal aging.” Ann Neurol 67:122 (2010).
  3. Herrup K. “The case for rejecting the amyloid cascade hypothesis.” Nat Neurol 18:794 (2016).
  4. Kumar DKV et al. “Amyloid-beta peptide protects against microbial infection in the mouse and worm models of Alzheimer’s disease.” Science Translational Medicine 8:340ra72 (2016).
  5. Backes WH et al. “Blood-brain-barrier leakage in patients with early Alzheimer’s disease.” Radiology doi.org/10.1148/radiol.2016152244 (2016).
  6. Wang W et al. “Resolution of inflammation is altered in Alzheimer’s disease.” Alzheimer’s and Dementia 11:40 (2015).
  7. Vandal M et al. “Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2.” J Neurochem 129:516 (2014).
  8. Cloughesy TF and Black KL. “Pharmacological blood-brain-barrier modification for selective drug delivery.” J Neuro-Oncology 26:125 (1995).
  9. Chouinard-Watkins R et al. “A diet rich in docosahexaenoic acid restores liver arachidonic acid and docosahexaenoic acid concentrations in mice homozygous for the human apolipoprotein E ϵ4 allele.” J Nutr doi:10.3945/jn.116.230052 (2016).
  1. Conquer JA et al. “Fatty acid analysis of blood plasma of patients with Alzheimer’s disease, other types of dementia, and cognitive impairment.” Lipids 35:1305 (2000).
  2. Bell L et al. “A Review of the Cognitive Effects Observed in Humans Following Acute Supplementation with Flavonoids, and Their Associated Mechanisms of Action.” Nutrients 7:10290 (2015).

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About Dr. Barry Sears

Dr. Barry Sears is a leading authority on the impact of the diet on hormonal response, genetic expression, and inflammation. A former research scientist at the Boston University School of Medicine and the Massachusetts Institute of Technology, Dr. Sears has dedicated his research efforts over the past 45 years to the study of lipids. He has published 40 scientific articles and holds 14 U.S. patents in the areas of intravenous drug delivery systems and hormonal regulation for the treatment of cardiovascular disease. He has also written 14 books, including the New York Times #1 best-seller "The Zone". His books have sold more than 6 million copies in the U.S. and have been translated into 22 different languages.


  1. L McCarley

    It is with gratitude I tank you. While we do our best, it’s only natural to be distracted by our well meaning doctors and advertising. In 1992, individual Cobra health insurance for a family was $7200/annually, and by 2012 the projected and actual costs were close, $30,000. Long-term care costs for a friend have doubled relatively over five years to $7,000/monthly now. Finally, insurers are offering incentives to employers of a healthier workforce, so their outlook is better in The Zone.

    • Barry Sears

      Your analysis of the growing economic burden of health care is correct. However, it is unclear if the insurers have enough insight to offer the correct incentives that will reduce that economic burden. Often it is a case of “shoot, ready, aim”.

  2. Andrew M

    Mr Sears I have read and listened to most of your books.Most notably the Omega RX Zone.At age 16 i was diagnosed with a Psychiatric illness which all specialists wrote me off.The medications i took made me sleep 10 hours a day and i felt more down.

    Ive been using your Omega 3s for some time now and its turned many things around.Your info has really helped me.

    Its true inflammation and reduced blood flow is the cause of many diseases.

    Now I’m healthy in mind and body and thats priceless.Nothing beats good old common sense nutrition.Keep up the good work!

  3. Janice Trodglen

    My husband has had 4colon surgeries in the last 5 years and 26 inches of his sigmoid colon removed. The cause was stretchy colon. A year after his first surgery he had a blood clot in the back of knee, took warfarin for a year. A year after his third surgery he developed another blood clot behind same knee. He is taking Xeralto. During this time he developed Parkinson’s disease with slight dementia, possibly Lewy Bodies.I desperately want to put him on your fish oil but I don’t know if I can with the blood thinner. What do you suggest? I am taking it for elevated cholesterol.Thank you for all you are doing to help us be well. My husband is 73.

    • Barry Sears

      This is why the AA/EPA test is so important to use to determine the optimal dosage. Keeping the AA/EPA ratio between 1.5 and 3 should not effect bleeding. This can be confirmed by your physician using a standard pro-thrombin test. But as always because your husband is taking a prescription drug, check with your physician first.

  4. Dr. Arcadio P. Sincero

    Dr. Sears,

    I have read several of your books about the Zone. I would say that they have helped improved my health tremendously. I am no longer taking my blood pressure and cholesterol maintenance medicines that I used to take for 37 years. I stopped them in 2013.

    Regarding your books, I am always confused about the following statement:

    “Good eicosanoids enhance the immune system while the bad ones depress it.”

    Does enhancing the immune system by good eicosanoids mean that the number of immune cells are increased? If so, why would omega-3, capable of producing good eicosanoids, alleviate arthritis when the number of immune cells are increased?

    On the other hand, does depressing the immune system by bad eicosanoids mean the number of immune cells are reduced? And, if so, how can bad eicosanoids be bad for arthritis when the number of immune cells are reduced?

    Thank you very much.

    • Barry Sears

      First I am glad to hear of your excellent experience with the Zone Diet.

      The immune system is tightly balanced by the constant initiation and resolution of inflammation. “Bad” eicosanoids keep the immune system constantly activated leading to organ damage and eventually loss of function. “Good” eicosanoids resolve the existing inflammation and bring the immune system back into a resting state. Thus eicosanoids function as “on” or “off” switches for the immune cells without affecting their numbers.

      Relative to arthritis, the “bad” eicosanoids derived from AA are overproduced causing the immune cells to continue to attackh the joint with a wide range of inflammatory mediators such as cytokines. This causes the pain. The “good” eicosanoids (i.e. resolvins) derived from EPA and DHA turn off the activity of the activated immune cells in addition to accelerlating the regeneration of new tissue by removing debris from damaged cells that can cause further initiation of immune attack.

      • Dr. Arcadio P. Sincero

        So, the “good” eicosanoids turning off the activated immune cells in addition to accelerating the regeneration of new tissue: Is this what is meant by enhancing the immune system?

        And, “bad” eicosanoids keep the immune system constantly activated leading to organ damage: Is this what is meant by depressing the immune system?

        Thank you very much.

  5. Joy

    This sounds great, but I’m in Australia. How does this work? Are samples processed locally?

    • Barry Sears

      I am not aware of any company in Australia that does this type of testing. The lab analysis for the test kit that we use is done in the U.S.

  6. Robin

    If an older parent is already showing signs of memory loss could this test help? I would much rather try supplements/diet to slow down process if possible than meds.

    • bsears@drsears.com

      The AA/EPA ratio has been found to elevated in individuals with Alzheimer’s or other dementias when compared to age-matched controls. I would recommend taking the Cellular Inflammation Test to determine the AA/EPA ratio. If it is high, then using a combination of high-dose fish and an anti-inflammatory diet would be good non-pharmacological combination to potentially improve mental cognition.

  7. Phyllis Botba

    This is so helpful. But I hate to read. How could you help someone like me!! What do I stay away from?? I have Familiar Medditerian Disease and I have to be careful of inflammation. So is it I should stay away from sugar and white flour?pkease give me specifics.
    I have been using Zone fish oil for 20 years.

    • Barry Sears

      I would eat primarily non-starchy vegetables balanced with low-fat protein and really cut back on omega-6 and saturated fatty acids.

  8. Paul Appleton

    Wishing you well always , love to read what you’re up to. Best and only rational/reasoned nutritional advice to take in the world.

  9. Barbara Upchurch

    I am going to get your book and try this for my husband starting tomorrow!!! Am praying your right !!

  10. Doug Brown Jr

    Quite an article indeed. Was wondering what your thoughts would be on how or if “earthing” would fit into the inflammation reduction equation for Alzheimer’s since it has a whole body effect???

    • Dr. Sears

      I believe diet will have a far greater impact on inflammation than walking barefoot. Nonetheless, walking without shoes for extended periods of time is reasonable.

  11. Maggie Ringsred

    You are awesome!
    This is great thinking – thank you for your uncompromised approach to bringing light into these important and complex discussions.

    • Dr. Sears

      The fun part of medicine is that it is constantly changing. Unfortunately, too many in the medical establishment seem to ignore that fact.

  12. Mark Mcginn

    Certainly a surprising indication, wow, Dr. Sears, you have been talking about resolution ,resolvins and scarring since 2005 in your book the Anti-inflammation Zone, p.232. If bacterial fragments/LPS, can enter a leaky BBB, what is the likely source of those fragments in the blood stream, a leaky gut ? and would short chain fatty acids like butyrate, produced by gut microbes, be helpful for improving BBB leakiness as well as the reduction of AA and increase in EPA ?

    • Barry Sears

      Sometimes you can be too far ahead of your time. It’s nice to long around long to see the picture emerge from the shadows.

      • Mark Mcginn

        It is nice to see after all these years that many are now talking about inflammation and the diet, polyphenols, fiber rich plant foods and omega 3’s.

        And 20 years from now will they be saying it’s not simply aging but unresolved inflammation that leads to a leaky BBB and alzheimers ?

        I hope we are here to see it and of sound mind.


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