Good find VOD,
My take on AD (Alzheimer's) is prevention, from what I've seen lower amounts of free T is the main culprit leading to AD risk (from this study) for older fellas.......there's other risks too.
For instance, family history. Meaning, if someone had AD in your family history your risk to develop AD is increased. A protein has been identified called APOEepsilon4 (apolipoprotein epsilon 4 (APOE epsilon 4):
Quote:found that both low serum testosterone and the interaction between testosterone and APOEepsilon4 were associated with AD. Furthermore, testosterone levels were lower in APOEepsilon4-positive controls (mean: 11.3 nmol/L) than in controls without the allele (19.1 nmol/L).
Sleep apnea: Recent studies found that the apolipoprotein epsilon 4 (APOE epsilon 4) allele increases the risk for sleep disordered breathing, particularly sleep apnea. The APOE epsilon 4 allele is associated with cognitive decline and the development of dementia in the general population as well as in patients with TB.
If you've been identified as a carrier of this gene your risk for developing AD increases (@ 29% I believe). So, I see a few options, keep SHBG (sex hormone binding globulin) balance. HIGH SHBG lowers free T, that's not good regardless, for either NBE/hrt too. Free T is the bioavailable part of total T......this part converts T into E. if this pool of free T is kept in the free range it serves two purposes related towards us I think....1) lowers risk of AD in older males and 2) converts T to E.
Back to prevention: keep serum lipids out of danger, (aka LDL) the bad cholesterol. Meaning eat good fats and stay away from TFA (trans fatty acids). Olive oil, coconut oil to replace trans fats....in moderation.
White Peony offers AD nuero-protection, see info below. Intercellular calcium signaling cascade are the next example of AD protection.....(though second messengers play a part with intracellular signaling):
Quote:Intracellular calcium signaling cascades play a pivotal role in ERα neuroprotection against AD. The ERα-mediated inhibition of Death domain-associated protein (Daxx) translocation and the combination of membrane ERα and caveolin in caveolae may protect against AD. Moreover, the voltage-dependent anion channel (VDAC)/ERα association may be important for maintaining channel inactivation and may be relevant in neuronal preservation against Aβ injury.
I see garlic can help prevent AD (promotes freeT), intermittent fasting (1-2 day fast lowers AD risk, exercise, vitamin D, leafy greens (vitamin K), others too.
Info on garlic:
Alzheimer’s Disease—Yes, It’s Preventable!
Exp Gerontol. 2004 Nov-Dec;39(11-12):1633-9.
Low free testosterone is an independent risk factor for Alzheimer's disease.
Hogervorst E1, Bandelow S, Combrinck M, Smith AD.
The purpose of this study was to assess pituitary gonadotropins and free testosterone levels in a larger cohort of men with Alzheimer's disease (AD, n=112) and age-matched controls (n=98) from the Oxford Project to Investigate Memory and Ageing (OPTIMA). We measured gonadotropins (follicle stimulating hormone, FSH, and luteinizing hormone, LH), sex hormone binding globulin (SHBG, which determines the amount of free testosterone) and total testosterone (TT) using enzyme immunoassays. AD cases had significantly higher LH and FSH and lower free testosterone levels. LH, FSH and SHBG all increased with age, while free testosterone decreased. Low free testosterone was an independent predictor for AD. Its variance was overall explained by high SHBG, low TT, high LH, an older age and low body mass index (BMI). In controls, low thyroid stimulating hormone levels were also associated with low free testosterone. Elderly AD cases had raised levels of gonadotropins. This response may be an attempt to normalize low free testosterone levels. In non-demented participants, subclinical hyperthyroid disease (a risk factor for AD) which can result in higher SHBG levels, was associated with low free testosterone. Lowering SHBG and/or screening for subclinical thyroid disease may prevent cognitive decline and/or wasting in men at risk for AD.
(14-09-2016, 11:10 PM)Lotus Wrote: Brain Res. 2015 Aug 27;1618:149-58. doi: 10.1016/j.brainres.2015.05.035. Epub 2015 Jun 3.
Paeoniflorin attenuates Aβ1-42-induced inflammation and chemotaxis of microglia in vitro and inhibits NF-κB- and VEGF/Flt-1 signaling pathways.
Liu H1, Wang J2, Wang J3, Wang P4, Xue Y5.
Alzheimer׳s disease (AD) is a neurodegenerative disease with elusive pathogenesis, which accounts for most cases of dementia in the aged population. It has been reported that persistent inflammatory responses and excessive chemotaxis of microglia stimulated by beta-amyloid (Aβ) oligomers in the brain may accelerate the progression of AD. The present study was conducted to explore whether paeoniflorin (PF), a water-soluble monoterpene glycoside isolated from the root of Paeonia lactiflora Pallas, could attenuate Aβ1-42-induced toxic effects on primary and BV-2 microglial cells in vitro. Our data showed that PF pretreatment inhibited Aβ1-42-induced production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in rodent microglia. Also, the nuclear translocation of nuclear factor kappa B (NF-κB) subunit p65 and the phosphorylation of NF-κB inhibitor alpha (IκBα) in Aβ1-42-stimulated microglial cells were suppressed by PF administration. Moreover, PF treatment reduced the release of chemokine (C-X-C motif) ligand 1 (CXCL1) and chemokine (C-C motif) ligand 2 (CCL-2) from Aβ1-42-stimulated microglia. Additionally, application of PF inhibited the increases in vascular endothelial growth factor (VEGF) and VEGF receptor 1 (Flt-1) triggered by Aβ1-42, and resulted in a concomitant reduction in microglial chemotaxis. Restoration of VEGF was noted to counteract the inhibitory effect of PF, suggesting that PF mitigated Aβ1-42-elicited microglial migration at least partly by suppressing the VEGF/Flt-1 axis. In summary, in presence of Aβ1-42, PF pretreatment inhibited the excessive microglial activation and chemotaxis.
The protein encoded by this gene is a major apoprotein of the chylomicron. It binds to a specific liver and peripheral cell receptor, and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. This gene maps to chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes. Mutations in this gene result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. [provided by RefSeq, Jun 2016]
Apolipoprotein E epsilon4 and testosterone interact in the risk of Alzheimer's disease in men.
Hogervorst E1, Lehmann DJ, Warden DR, McBroom J, Smith AD.
To assess the association between testosterone levels and APOEepsilon4 in cases with AD and controls.
We included 61 men with definite or probable Alzheimer's disease (AD) and 55 elderly male controls from the Oxford Project to Investigate Memory and Ageing (OPTIMA). Testosterone was measured using a competitive enzyme immunoassay (Bayer).
We found that both low serum testosterone and the interaction between testosterone and APOEepsilon4 were associated with AD. Furthermore, testosterone levels were lower in APOEepsilon4-positive controls (mean: 11.3 nmol/L) than in controls without the allele (19.1 nmol/L).
Low testosterone is potentially a modifiable risk factor, which may prove relevant to APOEepsilon4 carriers who are at risk of AD.
Sleep apnea, apolipoprotein epsilon 4 allele, and TBI: Mechanism for cognitive dysfunction and development of dementia
Ruth O'Hara, PhD;1-2* Avinoam Luzon, BS;2 Jeffrey Hubbard, BA;1-2 Jamie M. Zeitzer, PhD1-2
1Sierra-Pacific Mental Illness Research, Education, and Clinical Center, Department of Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; 2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA
Abstract — Sleep apnea is prevalent among patients with traumatic brain injuries (TBIs), and initial studies suggest it is associated with cognitive impairments in these patients. Recent studies found that the apolipoprotein epsilon 4 (APOE epsilon 4) allele increases the risk for sleep disordered breathing, particularly sleep apnea. The APOE epsilon 4 allele is associated with cognitive decline and the development of dementia in the general population as well as in patients with TBI. These findings raise the question of whether patients with TBI who are APOE epsilon 4 allele carriers are more vulnerable to the negative effects of sleep apnea on their cognitive functioning. While few treatments are available for cognitive impairment, highly effective treatments are available for sleep apnea. Here we review these different lines of evidence, making a case that the interactive effects of sleep apnea and the APOE epsilon 4 allele represent an important mechanism by which patients with TBI may develop a range of cognitive and neurobehavioral impairments. Increased understanding of the relationships among sleep apnea, the APOE epsilon 4 allele, and cognition could improve our ability to ameliorate one significant source of cognitive impairment and risk for dementia associated with TBI.
J Alzheimers Dis. 2015;43(4):1137-48. doi: 10.3233/JAD-141875.
Update on the neuroprotective effect of estrogen receptor alpha against Alzheimer's disease.
Lan YL1, Zhao J2, Li S1.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and disordered cognition. Women have a higher AD incidence than men, indicating that the declining estrogen levels during menopause may influence AD pathogenesis. However, the mechanism underlying estrogen's neuroprotective effect is not fully clarified and is complicated by the presence of several distinct estrogen receptor (ER) types and the identification of a growing number of ER splice variants. Thus, a deeper analysis of ERs could elucidate the role of estrogen in age-related cognitive changes. Intracellular calcium signaling cascades play a pivotal role in ERα neuroprotection against AD. The ERα-mediated inhibition of Death domain-associated protein (Daxx) translocation and the combination of membrane ERα and caveolin in caveolae may protect against AD. Moreover, the voltage-dependent anion channel (VDAC)/ERα association may be important for maintaining channel inactivation and may be relevant in neuronal preservation against Aβ injury. Additionally, ERα may prevent glutamate excitotoxic injury by Aβ through estrogen
signaling mechanisms. ERα and IGF-IR co-activation may mediate neuroprotection, and many other growth factors and intracellular signaling responses triggered by ERα may also play important roles in this process. Furthermore, details regarding the genes and mRNA variants of ERα that are expressed in different parts of the human organs have been clarified recently. Therefore, here we review the literature to clarify the neuroprotective role of ERα. This review focuses on the potential mechanisms mediated by ERα in the intracellular signaling events in nervous system cells, thereby clarifying ERα-mediated protection against AD.
Effects of a saturated fat and high cholesterol diet on memory and hippocampal morphology in the middle-aged rat.