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A new study has reported that the neuropathological pathways causing tau hyperphosphorylation typically associated with AD were also shown to be activated in COVID-19 patients (Reiken et al., 2022). The authors propose "that the alteration of cellular calcium dynamics due to leaky RyR2 in COVID-19 brains is associated with the activation of neuropathological pathways that are also found in the brains of AD patients."
This is yet more evidence implicating Gq/11 proteins."Future experiments will explore calcium channels as a potential therapeutic target for the neurological complications associated with COVID-19."
Gq/11 proteins are well-established to be the transducing G proteins for Ca(2+) mobilizing receptors and have been implicated in the pathophysiology of Alzheimer's Disease since the 1990s.
Activation of Gq/11 leads to initiation of the PLC/IP(3) pathway, thereby activating RyR, increasing intracellular calcium.
Gq/11 are the most important G-proteins stimulating phosphoinositide hydrolysis in the human brain (Pavia et al., 1998).
Fluoride poisoning may also produce identical neurological damage as is observed in AD. Fluoride poisoning is characterized by aberrant activation of G-protein-mediated pathways. Effects are bi-phasic, dependent on dose and duration, and are mediated mostly via thyroid hormone-regulated channels. Effects of fluoride on Gq/11 are well established.
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https://alz-journals.onlinelibrary.wile ... /alz.12558
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https://www.ncbi.nlm.nih.gov/labs/pmc/a ... MC6477877/
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"Conclusions: Thyroid hormones were moderately altered in mild AD dementia with increased serum FT4, and in addition, the reduced T3/T4 ratios may suggest decreased peripheral conversion of T4 to T3. Furthermore, serum T3 levels were related to brain structures involved in AD development."
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"These findings indicated that L-T4 increased BDNF and reelin protein expression by regulation of serum THs and TSH level in Aβ-induced AD rats."
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"AD patients with a blunted TSH response had a significantly higher mean free T4 (FT4) level (p less than 0.03) and tended to be more severely demented than those with a nonblunted response."
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" Message levels for a thyroid hormone receptor highly expressed in brain (c-ERB A alpha) was reduced by 52% in CA1 and 43% in CA2 in Alzheimer hippocampus as compared to Huntington controls."
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https://www.ncbi.nlm.nih.gov/labs/pmc/a ... MC3817016/
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"...plasma TSH concentrations were higher throughout the day in Alzheimer-type dementia (ATD) than in age-matched depressed patients (MDD), and plasma TSH concentrations were also higher throughout the day in female ATD compared with age-matched female control subjects."
Daimon CM, Chirdon P, Maudsley S, Martin B - "The role of Thyrotropin Releasing Hormone in aging and neurodegenerative diseases" Am J Alzheimers Dis (Columbia) 1(1):10.7726/ajad.2013.1003 (2013) doi: 10.7726/ajad.2013.1003
Other relevant literature
Rípová D, Platilová V, Strunecká A, Jirák R, Höschl C - "Alterations in calcium homeostasis as biological marker for mild Alzheimer's disease?" Physiol Res 53(4):449-52 (2004)
d'Uscio LV, Katusic ZS - "Vascular phenotype of amyloid precursor protein-deficient mice" Am J Physiol Heart Circ Physiol 316(6):H1297-H1308 (2019) doi: 10.1152/ajpheart.00539.2018
https://journals.physiology.org/doi/ful ... 00539.2018