Improving brain health - amyloid, tau, and energy
Neurological and neurocognitive diseases have often been associated with the peptide amyloid beta (AB) and considered a main culprit in the onset of Alzheimer’s disease (AD) due to its elevations in the central nervous system (CNS) or brain. Initial ideas behind AB accumulation were derived from Dr Alois Alzheimer’s observations in 1906 that peptide deposits, entangled structures and plaques were present in a patient with severe neurological and neurocognitive function. Much of the research over the last three decades has focused on AB which has two pathways, non amyloidogenic forming 3 soluble fragments and the amyloidogenic pathway providing the AB associated with AD (Gosztyla, Brothers, & Robinson, 2018).
The drugs don’t work they just make you worse but I know I’ll see your face again.
Despite many promising drugs, interventions ( y secretase inhibitors) focusing on lowering AB have been found to worsen cognitive function and increase susceptibility to infection (Penninkilampi, Brothers, & Eslick, 2016). Estrogen has often been touted as a protective hormone against both cardiovascular disease and cancers despite large bodies of conflicting and unsupportive data (Derwahl & Nicula, 2014)(Felty & Roy, 2005) (Benjamin, Toles, Seltzer, & Deutsch, 1993). In the last ten years or so further confusion has been added to most people’s (including doctors) understanding of estrogen and its so called protective mechanisms. In AD and dementia studies, estrogen was shown to decrease AB production, therefore it must be protective. The only downside to this observation is that it decreased AB, worsened cognition and increased susceptibility to infections (Gosztyla et al., 2018).
These observations tie in well to the current hypothesis that AB is found in most life forms, is protective, and increases as a form of anti-microbial action against certain agents such as viral and bacterial. Another interesting observation is the comparison between the actions of estrogen and progesterone in AD and dementia. Estrogen lowers AB but progesterone does not. Progesterone also decreases another key component of AD, a structure in the CNS called tau. Tau is a neuronal microtubule associated protein and a structural factor within the brain, which major functions are the promotion of self assembly and tau stabilisation (Carroll et al., 2007). The commonality of AD and dementia like states is tau aggregation and can be elevated in AD and also traumatic brain injury (TBI). Progesterone not only decreases damaged/entangled (hyperphosphorylated) tau it’s shown to be protective in TBI cases.
Increased estrogen is associated with increased excitability, seizures and neuronal degradation and this appears elevated in the premenstrual and estrous phases (Broestl et al., 2018). With increased aspects of pollution such as aluminium, mercury and cadmium and air and water borne pollutants that mimic estrogen, the potential of increased neurological damage is at an all-time high (Exley, 2013) (Annamalai & Namasivayam, 2015). Perhaps instrumental in the incidence and prevalence of neurological disease in the industrialised world?
Dietary fats, glucose and thyroid.
There’s far too much resistance in medicine to consider both neurological decline and diseases such as cancer as issues of metabolism. Mutations occur when biology degrades, when the mitochondrial aerobic function is compromised and there’s much that can be done to improve that area of function. The insistence that unsaturated fat is protective to neuronal structures appears problematic. In Parkinson’s disease for example degradation of polyunsaturated fats (both n3s and n6s) appears to increase lipid peroxidation, neuronal damage and that maintaining cholesterol levels appears to be protective (Alecu & Bennett, 2019). A common theme between all the neurological and oncological diseases is an abundance of PUFA and their oxidation, decreased glucose efficiency, decreased thyroid availability and mitochondrial damage(Schönfeld & Reiser, 2013)(Choi et al., 2017)
Some of the conflicts between the connection of low thyroid function and decreased neurological function are grounded in the persistence that biochemical evaluation of TSH and thyroid hormones (FT4 and FT3) are reliable and indicators of tissue saturation both in the hypothalamus, pituitary, neuronal and other tissues. Given the vast aspects of organisation allowed by adequate thyroid hormone and its effects on metabolism, movement, digestion, temperature, pulse rate, sleep, blood sugar, cholesterol and blood pressure, these variations might be of more value than reliance on poorly defined blood tests.
Endotoxin, gut and blood brain barrier.
Chronic digestive stress increases endotoxin, serotonin and histamine and can cross the blood brain barrier
Intestinal hyperpermeability or leaky gut syndrome has been very fashionable for the last ten years and holistic narratives of detoxing, raw green foods and probiotics seems to still be the Zeitgeist. Endotoxin or LPS (lipopolysaccharides) are well known to induce stress responses, stimulating the production of both serotonin and histamine and adrenal pathways. Histamine and serotonin can increase the permeability of the blood brain barrier to endotoxin induced increases of damaged tau structures is another aspect of neurological degradation(Wang et al., 2018). It also increases AB but know we have an idea that increasing AB is protective and it’s progression to plaques might be problematic. Attempting to lower AB is a reductionism that should best be avoided.
The concepts of detoxing and fasting might temporarily decrease endotoxin but they also have the capacity to make you colder, metabolically less efficient, decrease liver efficiency and lower thyroid hormone responsiveness that does not automatically increase after re-feeding (Boelen, Wiersinga, & Fliers, 2008). Ensuring adequate energy availability, endotoxin reducing foods like orange juice, carrots (Peat, 1997) (Ghanim et al., 2010) (Babic, Nguyen‐the, Amiot, & Aubert, 1994), and promoting restoring oxidative metabolism with compounds like methylene blue and caffeine (Eskelinen & Kivipelto, 2010)(Berrocal, Caballero-Bermejo, Gutierrez-Merino, & Mata, 2019), moderate exercise, engaging in life affirming activities and light exposure might be the some of the most effective factors in the fight against neurological disease.
References:
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