On 13th of Nov there were 566528 shares shorted and would think that today there are even less shorted. 1y ago there were 2.6M shorted so it looks like people are getting more understanding that value of Pran could get higher very quickly when it really starts.
As you may remember there was similar result in AIBL study (boow) and in the Imagine study there was a trend that PBT2 reduced the hippocampus atrophy speed in comparison to the placebos.
PLoS One. 2014 Jan 27;9(1):e86498. doi: 10.1371/journal.pone.0086498. eCollection 2014.
Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal Alzheimer's disease: a preliminary study.
Lim YY1, Villemagne VL2, Laws SM3, Ames D4, Pietrzak RH5, Ellis KA6, Harrington K1, Bourgeat P7, Bush AI1, Martins RN8, Masters CL1, Rowe CC9, Maruff P10; AIBL Research Group.
Alzheimers Res Ther. 2015 Nov 23;7(1):72. doi: 10.1186/s13195-015-0155-9.
Hippocampal atrophy but not white-matter changes predicts the long-term cognitive response to cholinesterase inhibitors in Alzheimer's disease.
Cheng YW1, Chen TF2, Cheng TW3, Lai YM4, Hua MS5, Chen YF6, Chiu MJ7,8.
This study aimed to investigate the feasibility of predicting the long-term effects of cholinesterase inhibitors (ChEI) with common clinical neuroimaging parameters of Alzheimer's disease, including medial temporal lobe atrophy (MTA) and white matter hyperintensity (WMH).
A cohort of 353 patients with very mild to moderate Alzheimer's disease received cholinesterase inhibitors and were followed for a median of 46.6 months. Baseline clinical data, including age, educational level, Clinical Dementia Rating (CDR), Taiwanese Mental State Examination (TMSE), and visual scoring for MTA and WMH were tested as possible predictive factors that influence the survival from a TMSE decline of at least 3 points.
During the follow-up period, 162(46 %) patients had a significant TMSE decline. Patients with age-adjusted prominent MTA had a significantly shorter TMSE-decline free interval than those without (43.4 ± 4.5 months vs. 68.2 ± 9.5 months, log rank test p-value =0.001). However, the severity of WMH does not significantly influence cognitive outcomes. Cox regression analysis identified that younger age at the time of starting ChEI (p
Go Prana's home page an then AGM webcast. There at 5min+ 10 sec Kempler tells....
Org Lett. 2015 Nov 20. [Epub ahead of print]
Synthesis of Denosomin-Vitamin D3 Hybrids and Evaluation of Their Anti-Alzheimer's Disease Activities.
Sugimoto K1, Yajima H1, Hayashi Y1, Minato D1, Terasaki S1, Tohda C1, Matsuya Y1.
As an extension of previously conducted studies on developing an anti-Alzheimer's disease agent, denosomin (1-deoxy-24-norsominone, an artificial inducer of neurite elongation), derivatives were designed and synthesized based on the hypothesis that our denosomin would exhibit axonal extension activity via a 1,25D3-membrane-associated, rapid response steroid-binding protein (1,25D3-MARRS) pathway. The biological assay revealed that the hybridization of characteristic δ-lactone in denosomin and the triene moiety in VD3 was effective to enhance the nerve re-extension activity in amyloid β (Aβ)-damaged neurons.
PLoS One. 2015 Nov 17;10(11):e0139395. doi: 10.1371/journal.pone.0139395.
Iron Chelation Inhibits Osteoclastic Differentiation In Vitro and in Tg2576 Mouse Model of Alzheimer's Disease.
Guo JP1,2,3, Pan JX1, Xiong L1,2, Xia WF1,4, Cui S1,4, Xiong WC1,2.
Patients of Alzheimer's disease (AD) frequently have lower bone mineral density and higher rate of hip fracture. Tg2576, a well characterized AD animal model that ubiquitously express Swedish mutant amyloid precursor protein (APPswe), displays not only AD-relevant neuropathology, but also age-dependent bone deficits. However, the underlying mechanisms remain poorly understood. As APP is implicated as a regulator of iron export, and the metal chelation is considered as a potential therapeutic strategy for AD, we examined iron chelation's effect on the osteoporotic deficit in Tg2576 mice. Remarkably, in vivo treatment with iron chelator, clinoquinol (CQ), increased both trabecular and cortical bone-mass, selectively in Tg2576, but not wild type (WT) mice. Further in vitro studies showed that low concentrations of CQ as well as deferoxamine (DFO), another iron chelator, selectively inhibited osteoclast (OC) differentiation, without an obvious effect on osteoblast (OB) differentiation. Intriguingly, both CQ and DFO's inhibitory effect on OC was more potent in bone marrow macrophages (BMMs) from Tg2576 mice than that of wild type controls. The reduction of intracellular iron levels in BMMs by CQ was also more dramatic in APPswe-expressing BMMs. Taken together, these results demonstrate a potent inhibition on OC formation and activation in APPswe-expressing BMMs by iron chelation, and reveal a potential therapeutic value of CQ in treating AD-associated osteoporotic deficits.
Anesthesiology. 2015 Nov 18. [Epub ahead of print]
Cerebrospinal Fluid Biomarker for Alzheimer Disease Predicts Postoperative Cognitive Dysfunction.
Evered L1, Silbert B, Scott DA, Ames D, Maruff P, Blennow K.
Postoperative cognitive dysfunction (POCD) affects 16 to 21% of the elderly 3 months after anesthesia and surgery and is associated with adverse outcomes. The exact cause of POCD remains unknown. The authors hypothesized that elderly individuals with Alzheimer disease (AD) neuropathology, identified by cerebrospinal fluid (CSF) analysis, would have increased the risk for POCD.
CSF samples were collected from 59 patients 60 yr or older who received combined spinal and general anesthesia for elective total hip replacement. Patients underwent neuropsychological testing preoperatively and at 7 days, 3 months, and 12 months postoperatively. POCD at 3 months and cognitive decline at 12 months were calculated by using the reliable change index. CSF amyloid β1-42 (Aβ1-42), total-tau, phosphorylated-tau, and neurofilament light were assayed with enzyme-linked immunosorbent assay methods.
POCD was identified in 5 of 57 patients (8.8%) at 3 months. For Aβ1-42, 11 patients were below the cut-point for AD neuropathology of whom 3 were classified with POCD (27.3%; 95% CI, 6.0 to 61%), whereas of the 46 patients above the cut-point, 2 were classified with POCD (4.3%; 95% CI, 0.5 to 14.8%) (P = 0.01). There was no significant difference in the incidence of POCD in relation to the cut-points for any of the other analytes.
Low CSF Aβ1-42 may be a significant predictor of POCD at 3 months. This indicates that patients with AD neuropathology even in the absence of clinically detectable AD symptoms may be susceptible to POCD.
Neuropsychology. 2015 Nov 16. [Epub ahead of print]
Sending Your Grandparents to University Increases Cognitive Reserve: The Tasmanian Healthy Brain Project.
Lenehan ME, Summers MJ, Saunders NL, Summers JJ, Ward DD, Ritchie K, Vickers JC.
Increasing an individual's level of cognitive reserve (CR) has been suggested as a nonpharmacological approach to reducing the risk for Alzheimer's disease. We examined changes in CR in older adults participating over 4 years in the Tasmanian Healthy Brain Project.
A sample of 459 healthy older adults between 50 and 79 years of age underwent a comprehensive annual assessment of current CR, neuropsychological function, and psychosocial factors over a 4-year period. The intervention group of 359 older adults (M = 59.61 years, SD = 6.67) having completed a minimum of 12 months part-time university study were compared against a control reference group of 100 adults (M = 62.49 years, SD = 6.24) who did not engage in further education.
Growth mixture modeling demonstrated that 44.3% of the control sample showed no change in CR, whereas 92.5% of the further education participants displayed a significant linear increase in CR over the 4 years of the study. These results indicate that older adults engaging in high-level mental stimulation display an increase in CR over a 4-year period.
Increasing mental activity in older adulthood may be a viable strategy to improve cognitive function and offset cognitive decline associated with normal aging.
YAHOO kicked a lot of messages also on other boards. I think it was some kind of a technical problem. Thank you for your short version, it is easy to compare 14 $ and 47 $.
Kempler tells in the webcast (05.10) that after the Reach2HD results they did more studies increasing the dosage and could repeat the cognition improvement effect by PBT2. Cognition improved more by bigger dosage. So this is the reason prana needs to get bigger dosage than 250mg.
Most likely the same will happen also in AD ????
Rosas et al published this free paper few years ago. It gives some understanding about how different areas have very different metal concentrations at least in HD. " Alterations in Brain Transition Metals in Huntington Disease An Evolving and Intricate Story".
H. Diana Rosas et al
In the Tanzi's AD model to me the most important issue perhaps is that brain cells significantly increased the cell viability after treated with PBT2. So the cells which could be just about to die could improve their function when getting their metal balance corrected by PBT2. So even improvement of the brain cell function is possible and the clinical studies confirm this: Improvement in cognition both in Euro study and in the HD study. Now we got clearly better pictures of these cognition results than earlier in the talk by Shoulson.
It looks that cognition improvement perhaps will only last as long there are these almost dead cells but when they have been saved the improvement stops, PBT2 does not wake up the dead brain cells but it can vitalise the almost dead cells.
Yes, normal baking yeast.
As most of you remember Tardiff et al ( including Susan Lindquist ) publised in 2012 a paper where they had tested (in vitro) over 200.000 different drugs and only clioquinols were found to be effective in various neurodegenerative problems. So these Tanzi's results could be expected but of course they are very valuable demonstrating more clearly the details in the degenerative process. In any case there are very few effective drugs when treating neurodegenerative diseases and only ones seem to be clioquinols as PBT2 with both clinical and in vitro evidence.
Mol Neurobiol. 2015 Nov 9. [Epub ahead of print]
Dietary Patterns and Risk of Dementia: a Systematic Review and Meta-Analysis of Cohort Studies.
Cao L1, Tan L2,3, Wang HF1, Jiang T4, Zhu XC1, Lu H1, Tan MS5, Yu JT6,7,8.
Dietary patterns and some dietary components have been linked with dementia. We therefore performed a meta-analysis of available studies to determine whether there is an association between diet and risk of dementia. We included eligible articles and estimated risk ratio (RR) with 95 % confidence intervals (95 % CIs). Finally, there were 43 trials that met the inclusion standard. Some food intake was related with decrease of dementia, such as unsaturated fatty acids (RR: 0.84, 95 % CI: [0.74-0.95], P = 0.006), antioxidants (RR: 0.87, 95 % CI: [0.77-0.98], P = 0.026), vitamin B (RR: 0.72, 95 % CI: [0.54-0.96], P = 0.026), and the Mediterranean diet (MeDi) (RR: 0.69, 95 % CI: [0.57-0.84], P
This is very significant drop IMO, looks like almost nobody is waiting to see pps to drop any further. Only 682.912 shorted on the 30th of Oct. and today it can be even lower. The usual level has been much over 1 M, mostly over 2M. This trend downwards started last summer and the speed in the end of Oct has been at it's best, almost 17%.
Nat Neurosci. 2015 Nov 9. doi: 10.1038/nn.4163. [Epub ahead of print]
Decreased amyloid-β and increased neuronal hyperactivity by immunotherapy in Alzheimer's models.
Busche MA1,2,3, Grienberger C1,4, Keskin AD1, Song B1, Neumann U5, Staufenbiel M6, Förstl H2, Konnerth A1,3.
Among the most promising approaches for treating Alzheimer´s disease is immunotherapy with amyloid-β (Aβ)-targeting antibodies. Using in vivo two-photon imaging in mouse models, we found that two different antibodies to Aβ used for treatment were ineffective at repairing neuronal dysfunction and caused an increase in cortical hyperactivity. This unexpected finding provides a possible cellular explanation for the lack of cognitive improvement by immunotherapy in human studies.
J Neurochem. 2015 Nov 6. doi: 10.1111/jnc.13425. [Epub ahead of print]
Iron neurochemistry in Alzheimer's disease and Parkinson's disease: targets for therapeutics.
Belaidi AA1, Bush AI1.
Brain iron homeostasis is increasingly recognized as a potential target for the development of drug therapies for aging-related disorders. Dysregulation of iron metabolism associated with cellular damage and oxidative stress is reported as a common event in several neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. Indeed, many proteins initially characterized in those diseases such as amyloid-β protein, α-synuclein and huntingtin have been linked to iron neurochemistry. Iron plays a crucial role in maintaining normal physiological functions in the brain through its participation in many cellular functions such as mitochondrial respiration, myelin synthesis, and neurotransmitter synthesis and metabolism. However, excess iron is a potent source of oxidative damage through radical formation and due to the lack of a body-wide export system, a tight regulation of its uptake, transport and storage is crucial in fulfilling cellular functions while keeping its level below the toxicity threshold. In this review, we discuss the current knowledge on iron homeostasis in the brain and explore how alterations in brain iron metabolism affect neuronal function with emphasis on iron dysregulation in Alzheimer's and Parkinson's diseases. Finally, we discuss recent findings implicating iron as a diagnostic and therapeutic target for Alzheimer's and Parkinson's diseases.
And it is not so only in rats but in humans:
Nat Commun. 2015 May 19;6:6760. doi: 10.1038/ncomms7760.
Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE.
Ayton S, Faux NG, Bush AI; Alzheimer's Disease Neuroimaging Initiative.
Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ɛ4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ɛ4 being the major genetic risk factor for AD.
copper, according what you write here it is very evident that you have never been in any scientific medical conference.