Alzheimer’s is not a simple disease and it has no single cause.  Not that you would know this by consuming media accounts of the latest research or drug trail or screaming headline like “fill-in-the-blank CAUSES Alzheimer’s.”  We are left with the impression that modern medicine has identified the single cause of the disease and is getting ever closer to a pill to cure it.  Moving past the noise and confusion to gain a clearer understanding of Alzheimer’s can be difficult.

Thankfully, Dr. Dale Bredesen, an MD and researcher at UCLA, has provided just that in his book “The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline,” published in August 2017.  He looks at his own evolving understanding of Alzheimer’s over the decades as he and his team made many ground-breaking discoveries.  Many of which were published in peer reviewed journals including his amazing results treating patients with Alzheimer’s.

Bredesen’s book is mind blowing.  I don’t think it is an exaggeration to say that while everyone else in the field of Alzheimer’s research is arguing over tree bark, Bredesen takes us high above the forest and points out the features that we’ve all been either ignoring or not seeing at all.  He explains a benevolence to amyloid plaque that is astounding, a laundry list of contributing factors to the disease that includes the usual suspects and some new ones (for me), and includes a clear and understandable program for preventing and treating the disease.  Finally, his hypothesis reaches the gold standard by, to my mind, successfully explaining the observed facts (and not just in limited circumstances).

Like so many groundbreaking discoveries it was not achieved by following a straight path of inquiry.  And that’s not to say that Dr. Bredesen was a maverick or contrarian on a mission to overturn the conventional wisdom.  Rather, he spent years in search of the “one protein” responsible for the disease.  His plan was then to find the “one drug” that would cure Alzheimer’s.  That approach is really no different from 99% of the research going on in the field today, but Bredesen changed his thinking a few years back.

Fortunately for us he possessed the right combination of traits to let go of his long held preconceptions and ask why, after years of trying, the data did not support the original hypothesis.  This is real science.  Not hammering square pegs into round holes, but figuring out why the pegs and holes are not how we thought they would be.

Armed with a greatly enhanced understanding of the underlying process (which will have to be the subject of another article), Dr. Bredesen was able to begin categorizing Alzheimer’s by symptoms and underlying causes.  It is hard to overstate how important this paradigm shift is to our approach to Alzheimer’s.  By comparing predispositions, environmental exposures, and symptoms among patients one can finally focus on an appropriate line of inquiry and intervention.

The Types of Alzheimer’s (plagiarized lightly edited from the book)

  1.  Inflammatory – This type runs in families and occurs more often in people who carry one or two ApoE4 alleles.  In people who carry two copies of E4, symptoms often begin in the late forties or fifties.  For people who carry one copy of E4, symptoms typically begin in the late fifties or sixties.  The hippocampus loses volume, but most other brain regions do not, at least early on.  The brain’s temporal and parietal regions, responsible for speech, calculation, recognition, and writing, use less glucose, an indication of reduced activity.  Telltale  biochemical markers include:
    1. Increase in C-reactive protein
    2. Decrease in the ratio of albumin to globulin
    3. Increase in interleukin-6
    4. Increase in TNF – alpha
    5. Accompanying metabolic and hormonal abnormalities such as insulin resistance.
  2. Atrophic – Also more frequent in those with E4, but typically initiates symptoms about a decade later than the inflammatory type.  Also presents with the loss of ability to form new memories even as the ability to speak, write, and calculate are retained.  No evidence of inflammation.  Instead the nutrients needed for brain synapse function have gone missing.
    1. Levels of hormones including thyroid, adrenal, estrogen, progesterone, testosterone, and pregnenolone are usually suboptimal.
    2. Vitamin D is often reduced.
    3. Insulin resistance may occur, or insulin levels may be too low.
    4. Homocysteine may be high (although homocysteine may also be increased in type 1).
  3. Glycotoxic – A combination of type 1 and 2 above.  Inflammation and reduced support for brain synapses.
    1. Glucose levels are chronically high, resulting in alteration to various protein (called glycation) and in inflammation, as in type 1.
    2. The high level of insulin secreted in response to the high glucose results in insulin resistance, so that insulin no longer works as well as a neurotrophic molecule, and this loss of trophic support is characteristic of type 2.
  4. Toxic or Vile – More common in those with ApoE3.  Typically no family history of Alzheimer’s.  Symptoms usually begin in the late forties to early sixties, often following great stress, and rather than beginning as memory loss, starts with cognitive difficulties involving numbers or speech or organizing.  Instead of the usual progression of Alzheimer’s this variation can wipe out old and new memories.  It’s less a progression than an all out assault on the brain.  This type is almost always misdiagnosed until a spinal tap or PET scan confirms Alzheimer’s.
    1. Many brain areas are atrophied.
    2. Neuroinflammation and vascular leak detected on FLAIR MRI.
    3. Low zink and high copper.  Copper:Zink ratio should be 1:1.  This type can have ratios more like 3.4:1
    4. Hormonal abnormalities, in which the system that responds to stress (the HPA axis) is dysfunctional.  This may show up in the lab tests as low cortisol, high reverse T3, low free T3, low pregnenolone, low estradiol, low testosterone, or other hormonal abnormalities.
    5. High blood levels of toxic chemicals such as mercury or of mycotoxins, which are produced by molds.

Bredesen’s book contains the best explanation of Alzheimer’s I have ever seen.  And these classifications of Alzheimer’s give patients, families, and doctors powerful information and a road map for prevention and treatment.  The days of palliative care for Alzheimer’s are numbered.  Herein lies hope.