{"id":769,"date":"2018-10-14T19:51:36","date_gmt":"2018-10-14T19:51:36","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=769"},"modified":"2018-10-15T03:27:29","modified_gmt":"2018-10-15T03:27:29","slug":"a-cure-for-alzheimers-yes-a-cure-for-alzheimers","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2018\/10\/14\/a-cure-for-alzheimers-yes-a-cure-for-alzheimers\/","title":{"rendered":"A cure for Alzheimer’s? Yes, a cure for Alzheimer’s!"},"content":{"rendered":"

This is the most important column I\u2019ve ever written. \u00a0The message is quite complex–dozens of new health parameters to test for and to optimize, all of them interacting in ways that will require new training for MDs. \u00a0The message is also as simple as it can be: There is a cure for Alzheimer\u2019s disease. You can stop reading right here, and buy two copies of Dale Bredesen\u2019s book, one for you and one for your doctor: \u00a0<\/i>The End of Alzheimer\u2019s<\/i><\/a>.<\/i><\/p>\n

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Dr Bredesen\u2019s spectacular success is easily lost in a flood of overly-optimistic, early hype about any number of magic cures. \u00a0This is an excuse for the New York Times, the Nobel Prize committee, and the mainstream of medical research, but it\u2019s no excuse for me. \u00a0I\u2019ve known Bredesen for 14 years, and I\u2019ve written about his work<\/a> in the past. \u00a0His book<\/a> has been out for a year, and I should have written this column earlier.<\/p>\n

I suspect you\u2019re waiting for the punch line: what is Bredesen\u2019s cure? \u00a0That\u2019s exactly what I felt when I read about his work three years ago. But there isn\u2019t a short answer. \u00a0That\u2019s part of the frustration, but it\u2019s also a reason that Bredesen\u2019s paradigm may be a template for novel research approaches cancer, heart disease, and aging itself.<\/p>\n\n\n\n
The Bredesen protocol consists of a battery of dozens of lab tests, combined with interviews, consideration of life style, home environment, social factors, dentistry, leaky gut, mineral imbalances, hormone imbalances, sleep and more. \u00a0This leads to an individual diagnosis: Which of 36 factors known to affect APP cleavage are most important in this particular case? How can they be addressed for this individual patient?<\/strong><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Brain cells have on their surface a protein called APP, which is a dependence receptor<\/a>. \u00a0It is like a self-destruct switch whose default is in the ON position. \u00a0The protein that binds to the receptor is a neurotrophin ligand, and in the absence of the neurotrophin ligand, \u00a0the receptor signals the cell to die.<\/p>\n

APP cleavage<\/a> is the core process that led Bredesen down a path to his understanding of the etiology of AD 16 years ago<\/a>. \u00a0APP is Amyloid Precursor Protein, and it is sensitive to dozens of kinds of signals, adding up the pros and the cons to make a decision, to go down one of two paths. \u00a0It can be cleaved in two, creating signal molecules that cause formation of new synapses and formation of new brain cells; or it can be cleaved in four, creating signal molecules that lead to trimming back of existing synapses, and eventually, to apoptosis, cell suicide of neurons.<\/p>\n

\"\"<\/p>\n

In a healthy brain, these two processes are balanced so we can learn new things and we can forget what is unimportant. \u00a0But in the Alzheimer\u2019s brain, destruction (synaptoclastic) dominates creation (synaptoblastic), and the brain withers away.<\/p>\n

On the right, one of the fragments is beta amyloid.\u00a0 Beta amyloid blocks the dependence receptor, so the receptor cannot receive the neurotrophin ligand that gives it permission to go on living. \u00a0Beta amyloid is one of the 4 pieces, when the APP molecule goes down the branch where it is split in 4.<\/p>\n

One of the signals that determines whether APP splits in 2 or in 4 is beta amyloid itself. \u00a0This implies a positive feedback loop; beta amyloid leads to even more beta amyloid, and in the Alzhyeimer\u2019s patient, this is a runaway process. \u00a0But positive feedback loops work in both directions–a boon to Bredesen\u2019s clinical approach. If the balance in signaling can be tipped from the right to the left pathway in the diagram above, this can lead to self-reinforcing progress in the healing direction. \u00a0In the cases where Bredesen\u2019s approach has led to stunning reversals of cognitive loss, this is the underlying mechanism that explains the success.<\/p>\n

Amyloid has been identified with AD for decades, and for most of that time the mainstream hypothesis was that beta-amyloid plaques cause the disease. \u00a0(Adherents to this view have been referred to jokingly as BAPtists.) But success in dissolving the plaques has not led to restored cognitive function<\/a>. \u00a0In Bredesen\u2019s narrative, generation of large quantities of beta amyloid are a symptom of the body\u2019s attempts to triage a dying brain.<\/p>\n

 <\/p>\n

To tip the balance back toward growing new synapses<\/b><\/p>\n

Having identified the focal point that leads to AD, Bredesen went to work first in the lab, then in the clinic, to identify processes that tend to tip the balance one way or the other. \u00a0He has compiled quite a list.<\/p>\n\n\n\n
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  • Reduce APP\u03b2-cleavage<\/li>\n
  • Reduce \u03b3-cleavage<\/li>\n
  • Reduce caspase-6 cleavage<\/li>\n
  • Reduce caspase-3 cleavage
    \n(All the above are cleavage in 4<\/i>)<\/li>\n
  • Increase \u03b1-cleavage (cleavage in 2<\/i>)<\/li>\n
  • Prevent amyloid-beta oligomerization<\/li>\n
  • Increase neprilysin<\/li>\n
  • Increase IDE (insulin-degrading enzyme)<\/li>\n
  • Increase microglial clearance of A\u03b2<\/li>\n
  • Increase autophagy<\/li>\n
  • Increase BDNF (brain-derived neurotropliic factor)<\/li>\n
  • Increase NGF (nerve growth factor)<\/li>\n
  • Increase netrin-1<\/li>\n
  • Increase ADNP (activity-dependent neuroprotective protein)<\/li>\n
  • Increase VIP (vasoactive intestinal peptide)<\/li>\n
  • Reduce homocysteine<\/li>\n
  • Increase PPZA (protein phosphatase 2A) activity<\/li>\n
  • Reduce phospho-tau<\/li>\n
  • Increase phagocytosis index<\/li>\n
  • Increase insulin sensitivity<\/li>\n
  • Enhance leptin sensitixity<\/li>\n
  • improve axoplasmic transport<\/li>\n
  • Enhance mitochondnal function and biogenesis<\/li>\n
  • Reduce oxidative damage and optimize ROS (reactive oxygen species) production<\/li>\n
  • Enhance cholinergic neurotransmission<\/li>\n
  • Increase synaptoblastic signaling<\/li>\n
  • Reduce synaptoclastic signaling<\/li>\n
  • Improve LTP (long-term potentiation)<\/li>\n<\/ul>\n<\/td>\n
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