Cable News and News About Your Cables (Neurons)

By Dale Bredesen, M.D., Chief Scientific Officer for Apollo Health

As you may have read, Ted Turner, founder of CNN (Cable News Network), passed away recently after years with Lewy body dementia. There are approximately one million Americans with Lewy body dementia (the three most common types of dementia are Alzheimer’s, vascular dementia, and Lewy body dementia), and the parallels with Alzheimer’s have turned out to be both revealing and truly remarkable:

• In Alzheimer’s, insults such as viruses, bacteria, and fungi are countered by the anti-microbials amyloid-beta and phospho-tau.
• In Lewy body dementia, insults such as viruses, bacteria, and fungi are countered by the anti-microbial alpha-synuclein.
• In Alzheimer’s, the amyloid is particularly potent at killing neurotropic DNA viruses of the Herpes family, such as HSV-1 and HHV-6A.
• In Lewy body dementia, the synuclein is particularly potent at killing neurotropic RNA viruses of the Arbovirus family, such as West Nile Virus and VEEV (Venezuelan Equine Encephalitis Virus).
• In Alzheimer’s, the amyloid also sequesters and inactivates bacteria such as E. coli.
• In Lewy body dementia, the synuclein also sequesters and inactivates bacteria such as E. coli.
• In Alzheimer’s, the amyloid also sequesters and inactivates fungi such as Candida.
• In Lewy body dementia, the synuclein also sequesters and inactivates fungi such as Aspergillus.
• In Alzheimer’s, the amyloid is considered to be part of the innate immune response.
• In Lewy body disease, the synuclein is considered to be part of the innate immune response.
• In Alzheimer’s, the amyloid inhibits mitochondrial function and leads to neurodegeneration.
• In Lewy body disease, the synuclein inhibits mitochondrial function and leads to neurodegeneration.
• In Alzheimer’s, the amyloid compromises insulin sensitivity directly by interacting with the insulin receptor.
• In Lewy body disease, the synuclein compromises insulin sensitivity indirectly by reducing the signaling of the insulin receptor’s main partner, IRS-1 (via TSC2).
• In Alzheimer’s, amyloid binds metals such as copper and zinc.
• In Lewy body dementia, synuclein binds metals such as copper and zinc.
• In Alzheimer’s, amyloid has a pro-inflammatory effect that is balanced by the related anti-inflammatory sAPPalpha.
• In Lewy body dementia, alpha-synuclein has a pro-inflammatory effect that is balanced by the related anti-inflammatory beta-synuclein.
• The pro-inflammatory effect in Alzheimer’s is mediated in large part via the NLRP3 inflammasome, activating microglia (to become M1 inflammatory microglia) and astrocytes.
• The pro-inflammatory effect in Lewy body dementia is mediated in large part via the NLRP3 inflammasome, activating microglia (to become M1 inflammatory microglia) and astrocytes.
• In Alzheimer’s, the amyloid binds to complement C1q as part of its pro-inflammatory effect.
• In Lewy body disease, the synuclein binds to complement C1q as part of its pro-inflammatory effect.
• In Alzheimer’s, the amyloid is prionic, i.e., it has the ability to beget more of itself via interactions with cellular proteins.
• In Lewy body dementia, the synuclein is prionic, i.e., it has the ability to beget more of itself via interactions with cellular proteins.
• Alzheimer’s pathophysiology includes direct ties to the cytoskeleton, which provides shape, stability, and neurite outgrowth/retraction. This occurs via tau, which stabilizes microtubules through an interaction with tubulin.
• Lewy body pathophysiology includes direct ties to the cytoskeleton, which provides shape, stability, and neurite outgrowth/retraction. This occurs via synuclein, which stabilizes microfilaments through an interaction with actin.
• In Alzheimer’s, various cellular insults cause phosphorylation of tau, and the resulting p-tau leads to disruption of the cytoskeletal microtubules.
• In Lewy body dementia, various cellular insults cause phosphorylation of synuclein, and the resulting p-synuclein leads to disruption of the cytoskeletal microfilaments.
• In Alzheimer’s, phosphorylation of tau is carried out largely by GSK-3beta, which is activated by stress.
• In Lewy body dementia, phosphorylation of synuclein is carried out largely by PLK2, which is activated by stress.
• In Alzheimer’s, DNA damage induces ApoE, which binds to DNA (especially ApoE4) and impacts gene expression, especially relevant to inflammation.
• In Lewy body dementia, DNA damage induces synuclein, which binds to DNA and impacts gene expression, especially relevant to DNA repair.
• ApoE4 may cycle on and off DNA, mediated by methylation (or a methylating enzyme).
• Synuclein may cycle on and off DNA, mediated by phosphorylation.
• In Alzheimer’s, the neurotransmitter acetylcholine, which is critical for memory formation, is markedly reduced, and other neurotransmitters such as dopamine are reduced to a lesser extent.
• In Lewy body dementia, the neurotransmitter acetylcholine, which is critical for memory formation, is markedly reduced, and other neurotransmitters such as dopamine are reduced to a lesser extent.
• In Alzheimer’s, amyloid interferes with neurotransmission, reducing release of acetylcholine.
• In Lewy body dementia, synuclein interferes with neurotransmission, reducing release of acetylcholine.
• In an effort to treat Alzheimer’s by increasing the neurotransmitter acetylcholine, cholinesterase inhibitors such as donepezil (Aricept) have been used, but while these may provide short-term improvements in some patients, the disease process is not affected, and there is no long-term benefit.
• In an effort to treat Lewy body dementia by increasing the neurotransmitter acetylcholine, cholinesterase inhibitors such as donepezil (Aricept) have been used, but while these may provide short-term improvements in some patients, the disease process is not affected, and there is no long-term benefit.
• The most successful treatment of Alzheimer’s to date has been to identify the various insults — such as pathogens, toxins, metabolic dysfunction, gut damage, sleep apnea, vascular disease, etc. — and address these with a precision medicine protocol like ReCODE. Although we have just completed a successful randomized controlled trial, more data are always helpful.
• The most successful treatment of Lewy body dementia to date has been to identify the various insults — such as pathogens, toxins, metabolic dysfunction, gut damage, sleep apnea, vascular disease, etc. — and address these with a precision medicine protocol like ReCODE. Although we have not yet done a randomized controlled trial, anecdotes of success have been noted, and more data will be important to collect.

Victims of Lewy body dementia now include Robin Williams, Glen Campbell, and Ted Turner, among many others. Let’s put an end to this horrific disease.