Traumatic Brain Injuries, Alzheimer’s Diseases and Tau Protein Dysfunctions. 

Evidence keeps piling up showing that Traumatic Brain Injuries (TBIs) from house falls, car and bicycle accidents, military exercises and sports like American football are increasingly leading to dementia, Alzheimer’s Diseases and other cognitive disorders. In this piece, i will first look at the scientific litterature that shows the existence of a causal relationship between TBIs and dementia. (Section A). Thereafter, i will examine pathophysiology and mechanisms (Section B) and wrap up with a word on how holistic medicine can help to promote neurogenesis and some semblance of brain recovery for the patients who have been diagnosed with TBI’s and Alzheimer’s Disease. (Section C)

 Section A

Traumatic Brain Injuries and Alzheimer’s Disease

Researchers from the University of Helsinki and the Helsinki University Hospital recently published a study that substantiates the relationship between TBIs and degenerative brain diseases. Encompassing the entire Finnish population, this study combined several nationwide registers to monitor more than 40,000 working-age adults, who survived the initial TBI, for ten years. Importantly, the persons´ level of education and socioeconomic status were accounted for.

“It seems that the risk for developing dementia after TBI is the highest among middle-aged men. The more severe the TBI, the higher the risk for subsequent dementia. While previous studies have identified good education and high socioeconomic status as protective factors against dementia, we did not discover a similar effect among TBI survivors”.  (Rahul Raj, docent of experimental neurosurgery and one of the primary authors of the study) (1). (Source)

Supporting these findings, in a 2015 Univeristy of Edinburg study, scientists have shown that People who have previously experienced severe head or whiplash injuries in the past have been shown to be at greater risk of developing dementia and Alzheimer’s Disease.  (2) (Source)

Close to twenty years before these two studies, Researchers had also found that any medical history of head injury more than doubled both the risk of developing Alzheimer’s disease and the chances of developing non-Alzheimer’s dementia, even after adjustment for the effects of age. (3) (Source)

The findings showed that the worse the head injury, the higher the risk of Alzheimer’s disease. Moderate head injury was associated with a 2.3-fold increase in risk, whereas severe head injury more than quadrupled the risk. (4)

The evidence shows that even mild traumatic brain injury can be a significant dementia risk if repetitive, like in American footbal or concussive force of military blasts. Indeed, repetitive mild traumatic brain injury is now recognized as an issue in contact sports, (5) (Source) especially American football as well as the concussive force of military blasts. (5, 6) (Source)   Indeed, these violent sport  traumas can lead to chronic traumatic encephalopathy (CTE), which is characterized by fibrillar tangles of hyperphosphorylated tau(Source). (7). High levels of tau protein in fluid bathing the brain are linked to poor recovery after head trauma (8) (Source).

Section B

Mechanisms and Tau Proteins

Insofar as pathophysiology is concerned, different mechanisms have been identified.  One Research Team has concluded that dementia may be precipitated by an immune reaction (inflammation) that occurs following head injury. Such inflammation can lead to formation of the toxic clumps of the amyloid and tau proteins that are hallmarks of Alzheimer’s disease. (2) (Source)

Given what we know about holistic medicine and lifestyle prevention, it’s reasonable to assume that inappropriate mainstream diets, stress, toxicity (including heavy metals) and other deleterious lifestyle elements may be contributing factors to the TBI-dementia phenomenon.

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Top: Neurons were grown in tissue culture and stained with antibody to MAP2 protein in green and MAP tau in red using the immunofluorescence technique. MAP2 is found only in dendrites and perikarya, while tau is found not only in the dendrites and perikarya but also in axons. As a result, axons appear red while the dendrites and perikarya appear yellow, due to superimposition of the red and green signals. DNA is shown in blue using the DAPI stain which highlights the nuclei: image public domain via c.c.

Tau Protein Abnormalities and  Hyperphosphorylation

Tau proteins are proteins that stabilize microtubules. They are abundant in neurons of the central nervous system. (9) They are also known as a highly soluble microtubule-associated protein (MAP) (Source). Pathologies of the nervous system such as Alzheimer’s disease and Parkinson’s disease are associated with tau proteins misfolding abnormalities, when they become so defective that they can no longer stabilize microtubules. (10) When misfolded, this otherwise soluble protein can form insoluble aggregates that contribute to a number of neurodegenerative diseases

Traumatic brain injuries can thus promote this misfoldment-based tau dysfunction, one element of which is associated to hyperphosphorylation. (11) Hyperphosphorylation of the tau protein can result in the self-assembly of tangles of paired helical filaments and straight filaments, which are involved in the pathogenesis of Alzheimer’s disease, frontotemporal dementia, and other tau related disorders. (12)

The data shows that hyperphosphorylated tau disassembles microtubules and sequesters normal tau, MAP 1(microtubule associated protein1), MAP 2, and ubiquitin into tangles of PHFs. This insoluble structure damages cytoplasmic functions and interferes with axonal transport, which can lead to cell death and Alzheimers. (13) (Source) Research also suggests that in Alzheimer’s disease, tau may be released extracellularly by an exosome-based mechanism. (14)

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Section C

Holistic Solutions

Safe and efficient holistic solutions need to be personalized to each Alzheimer’s patient, in particular, each patient needs to be tested so that the clinician can determine  what is affecting the brain’s plasticity signaling network. As the Institute’s workshop shows, the following lifestyle elements are essential to kick-start A.D. reversal and tau regularization. 1. Improved Mediterranean Diet and-or improved vegan diet, depending on the patient. 2. Circadian rigor, with deep sleep patterns. 3. Stress management via meditation, yoga and the like. 4. Supplementation: Taking melatonin, methylcobalamin, vitamin D3, fish oil and coenzyme Q10 each day. 5. Optimizing oral hygiene by using an electric flosser and electric toothbrush. 6. Hormonal boosting techniques. 7. Intermittent fasting. By following this core program, the Buck Institute was able to reverse the Alzheimer’s process in 9 out of 10 patients, even those with homozygous and  heterozygous ApoE4+. It published its results in 2014 (See the Institute’s Bredensen Protocol page). in 2015, Rush Univeristy carried out a complementary study on a much larger group of elderly people that showed a substantial reduction in Alzheimer’s risk. And from 2012 to 2017, the Happiness Medicine Institute conducted in depth research and some clinical practice that tweaked the “Alzheimer Reversal Code” even further, included, but not limited with special diets, coconut oil, different herbs, essential oils, minerals, (e.g., among others, magnesium) (15) probiotics and berries, in particular the berries that the Institute cultivates at the Mediterranean Holistic rejuvenation Center. (16) (See the Institute’s Workshops and pending ebook on this topic).

Discussion

Mild traumatic brain injuries are heterogeneous and highly individualized injuries. Recovery and return to pre-injury functioning is influenced by numerous factors. Given the brain’s neuro-plasticity,  affected cells can recover and new brain cells can be spurred to grow.  The primary pathophysiologies include ionic shifts, abnormal energy metabolism, tau abnormalities, diminished cerebral blood flow, and impaired neurotransmission.

It is important to appreciate that cell death is closely related to injury severity. Mild traumatic brain injuries, especially injuries on the milder end of the spectrum, are typically characterized by cellular dysfunction that is reversible.

However, what distinguishes a TBI that will lead to Alzheimer’s Disease from one that will not depends not only on the severity of the TBI and genetic predisposition, but also on the patient’s  age, (17) toxicity level, exercises, diets, sleep pattern, toxicity load and other lifestyle elements. (18) Head injuries are more likely to lead to Alzheimer’s disease in later life if the person has the apolipoprotein E (APOE) gene.

It appears that not enough research has been conducted to see if single head injuries resulting in unconsciousness for less than half an hour pose a definite risk for Alzheimer’s disease or other forms of dementia.  But repeated head injuries like in American football, European rugby and boxing have been shown to significantly promote cognitive dysfunction that favor Alzheimer’s, Parkinson’s and other neuro-degenertive diseases.

.As for the Tau question, one of the best Tau hypothesis states that excessive or abnormal phosphorylation of tau results in the transformation of normal adult tau into abnormal PHF-tau (paired helical filament) and NFTs (neurofibrillary tangles). The process of tau aggregation in the absence of mutations does not appear to be presently known. But we hypothesize that it might result from increased phosphorylation, protease action or exposure to polyanions, such as glycosaminoglycans. (19)

Conclusion

“It is a tragedy when an adult of working age develops dementia after recovering from a brain injury, not just for the patient and their families, but it also negatively impacts the whole society. In the future, it will be increasingly important to prevent TBIs and to develop rehabilitation and long-term monitoring for TBI patients,” (PLOS Medicine, 2017; 14 (7))

The WHO has predicted that TBI will become a leading cause of death and long-term illness during the next ten years. Already one per cent of the population in the United States suffers from a long-term disability caused by TBI. And Alzheimer’s Disease now affects close to 50 percent of Americans who reach their 80s. Approximately 5.4 million American patients and 30 million are affected globally (20) In the absence of effective prevention and holistic treatments, by 2050, at least 13 million Americans and 160 million globally will needlessly suffer and die  from this disease, burdening even more the Medicare system. Unlike several other chronic illnesses, Alzheimer’s disease prevalence is skyrocketing, which makes the need to develop effective prevention and treatment increasingly pressing. Recent estimates suggest that AD has become the third leading cause of death in the United States, behind cardiovascular disease and cancer. (21)  To make matters worse, women are at the epicenter of the Alzheimer’s epidemic, with 65% of AD patients and 60% of caregivers being women (22). Indeed, a woman’s chance of developing AD is now greater than her chance of developing breast cancer. (23)

Those in charge of public policy should thus invest not only in better regulating violent sports, military traumatizing activites, chronic stress, generalized toxicity and, inter alia, processed foods, but the Government should also promote cost-friendly preventive measures and holistic treatment plans via rehabilitation and rejuvenation centers where both TBI and Alzheimer’s patients can start holistic rejuvenation programs that will in the end not only alleviate lots of un-necessary suffering, but also save hundreds of billion of dollars that could be better invested in Life, longevity and prosperity.

Christian Joubert (HMI director and CSO)

Reference Notes

(1). Rahul Raj, Jaakko Kaprio, Miikka Korja, Era D. Mikkonen, Pekka Jousilahti, Jari Siironen. Risk of hospitalization with neurodegenerative disease after moderate-to-severe traumatic brain injury in the working-age population: A retrospective cohort study using the Finnish national health registriesPLOS Medicine, 2017; 14 (7): e1002316 DOI: 10.1371/journal.pmed.1002316
(2).https://www.alzheimers.org.uk/info/20053/research_projects/1058/is_there_a_link_between_head_injury_and_dementia
(3).  Neurology 2000;55:1158-66.
(4). Ibid
(5).Omalu, Bennet I. (July 1, 2005). “Chronic Traumatic Encephalopathy in a National Football League Player”Neurosurgery. 57: 128–134. doi:10.1227/01.NEU.0000163407.92769.EDPMID 15987548. https://doi.org/10.1227/01.NEU.0000163407.92769.ED
(6).  Goldstein LE, Fisher AM, Tagge CA, Zhang XL, Velisek L, Sullivan JA, et al. (May 2012). “Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model”Science Translational Medicine. 4 (134): See also DeWitt DS, Prough DS. Traumatic cerebral vascular injury: the effects of concussive brain injury on the cerebral vasculature. J Neurotrauma 2003;20:795-825. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739428
(7). McKee AC, Stern RA, Nowinski CJ, Stein TD, Alvarez VE, Daneshvar DH, et al. (January 2013). “The spectrum of disease in chronic traumatic encephalopathy”Brain. 136 (Pt 1): 43–64. doi:10.1093/brain/aws307PMC 3624697 . PMID 23208308.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624697
(8). Magnoni S, Esparza TJ, Conte V, Carbonara M, Carrabba G, Holtzman DM, Zipfel GJ, Stocchetti N, Brody DL (April 2012) [first published online November 24, 2011]. “Tau elevations in the brain extracellular space correlate with reduced amyloid-β levels and predict adverse clinical outcomes after severe traumatic brain injury”Brain. 135 (Pt 4): 1268–80. doi:10.1093/brain/awr286PMC 3326246 . PMID 22116192Lay summary – Washington University in St. Louis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326246
(9). Shin RW, Iwaki T, Kitamoto T, Tateishi J (May 1991). “Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer’s disease brain tissues”. Lab. Invest. 64 (5): 693–702.
(10). Lei P, Ayton S, Finkelstein DI, Adlard PA, Masters CL, Bush AI (November 2010). “Tau protein: relevance to Parkinson’s disease”. Int J Biochem Cell Biol. 42 (11): 1775–1778. doi:10.1016/j.biocel.2010.07.016PMID 20678581
(11). Hyperphosphorylation occurs when a biochemical with multiple phosphorylation sites is fully saturated. Hyperphosphorylation is one of the signaling mechanisms used by the cell to regulate mitosis. When these mechanisms fail, developmental problems, brain disorders and cancer are likely outcome. The dynamics of mitosis are similar to security system. In a healthy cell, checkpoints between phases permit a new phase to begin only when the previous phase is complete and successful. At these checkpoints, gatekeeper molecules block or allow events, depending on their level of phosphorylation. Kinases are responsible for adding phosphate groups and phosphatases for removing them.
(12).  Alonso A, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K (June 2001). “Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments”Proc. Natl. Acad. Sci. U.S.A. 98 (12): 6923–8. doi:10.1073/pnas.121119298PMC 34454 . PMID 11381127.
(13). Mudher M, Lovestone S (2002). “Alzheimer’s disease: do tauists and Baptists finally shake hands?”. Trends in Neurosciences25: 22–6. https://www.ncbi.nlm.nih.gov/pubmed/11801334
(14). Hall, G.F. (2011) Tau misprocessing leads to non-classical tau secretion via vesicle release – implications for the spreading of tau lesions in AD Int Conf. Alz Dis. meeting Paris, France See also: Saman, S. and Hall, G. F. (2011) Tau secretion from M1C human neuroblastoma cells occurs via the release of exosomes. Keystone Meeting on Neurodegenerative diseases, Feb 2011, Taos NM
(15). Lee JS, Han YM, Yoo do S, Choi SJ, Choi BH, Kim JH, Kim YH, Huh PW, Ko YJ, Rha HK, Cho KS, Kim DS. A molecular basis for the efficacy of magnesium treatment following traumatic brain injury in rats. J Neurotrauma 2004;21:549-561.
(16) Morris MC, Tangney CC, Wang Y, et al. MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimers Dement. 2015;11(9):1007-14.
(17). Dementia is commonly seen as a problem of the elderly. However, the Finnish study shows that TBI may cause dementia to develop before old age, and that dementia caused by injuries are much more common than was thought
(18).In patients with MTBIs, the brain undergoes dynamic restoration in the first two weeks post injury. The patient typically experiences maximal symptoms and problems within the first 72 hours with rapid improvement in functioning over the first two weeks. Athletes typically report resolution of symptoms within 2-21 days. Trauma patients typically take longer to return to their baseline functioning, but most recover within three months post injury. Some take considerably longer to recover. This can be due to a variety of factors, only some of which relate to the actual injury to the brain. Permanent damage to the brain occurs in some patients who sustain MTBIs, but the majority of the pathophysiology is neurometabolic and reversible.
(19). Lei P, Ayton S, Finkelstein DI, Adlard PA, Masters CL, Bush AI (November 2010). “Tau protein: relevance to Parkinson’s disease”. Int J Biochem Cell Biol. 42 (11): 1775–1778. doi:10.1016/j.biocel.2010.07.016PMID 20678581.
(20). Prince MA, Emiliano, Guerchet, Maëlenn, Prina, Matthew. 2014; World Alzheimer Report 2014 United Kingdom: Alzheimer’s Disease International.
(21). James BD, Leurgans SE, Hebert LE, Scherr PA, Yaffe K, Bennett DA. Contribution of Alzheimer disease to mortality in the United States. Neurology. 2014; 82:1045-1050. [PubMed]
(22). Shriver M. A Woman’s Nation Takes on Alzheimer’s. 2010;
(23). Special Report on Women and Alzheimer’s Disease. 2014; 1-80.
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Disclaimer: Nothing is this educational blog should be construed as medical advise
2017 (c) Happiness Medicine Institute and agents. All rights reserved

Professor Joubert teaches how to extend a healthy cancer-free Lifespan to 122 years thanks to safe, efficient and cost friendly breakthrough protocols. Working on a documentary and book that redefines Medicine in light of new discoveries, ancient wisdoms, innovative research and holistic science, he can be nonetheless available to coach patients back to homeostasis, wellbeing & Joie de Vivre. On occasion, Pr. Joubert can also coach health professionals to better protect their holistic practice when they must deviate from outdated and-or irrational mainstream “standards of care” in order to genuinely serve their patients, evidence-strong Science and internationally recognized human rights. For details, see the links called “Contact” and “Mission” (under the “About” link).

Posted in Neuro-science, Mental Disorders, Happiness & Joie de Vivre Medicine

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