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pivalde 126 posts  |  Last Activity: 6 hours ago Member since: Feb 15, 2001
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  • J Neurosci. 2015 Mar 25;35(12):4857-68. doi: 10.1523/JNEUROSCI.4989-14.2015.

    Tau immunotherapy modulates both pathological tau and upstream amyloid pathology in an Alzheimer's disease mouse model.

    Castillo-Carranza DL1, Guerrero-Muñoz MJ1, Sengupta U1, Hernandez C1, Barrett AD2, Dineley K1, Kayed R3.

    In Alzheimer's disease (AD), the pathological accumulation of tau appears to be a downstream effect of amyloid β protein (Aβ). However, the relationship between these two proteins and memory loss is unclear. In this study, we evaluated the specific removal of pathological tau oligomers in aged Tg2576 mice by passive immunotherapy using tau oligomer-specific monoclonal antibody. Removal of tau oligomers reversed memory deficits and accelerated plaque deposition in the brain. Surprisingly, Aβ*56 levels decreased, suggesting a link between tau and Aβ oligomers in the promotion of cognitive decline. The results suggest that tau oligomerization is not only a consequence of Aβ pathology but also a critical mediator of the toxic effects observed afterward in AD. Overall, these findings support the potential of tau oligomers as a therapeutic target for AD.

  • Reply to

    Tau paper from Mayo Clinic

    by pivalde Mar 29, 2015 3:42 AM
    pivalde pivalde Mar 29, 2015 3:52 AM Flag

    IMO it is good to read the paper below exlaining zinc and Tau. It is a free paper by Tanzi et al

    PLoS One. 2012; 7(3): e33552.

    Published online 2012 Mar 23. doi: 10.1371/journal.pone.0033552

    PMCID: PMC3311647

    The Zinc Dyshomeostasis Hypothesis of Alzheimer's Disease

    Travis J. A. Craddock,1,* Jack A. Tuszynski,1,2 Deepak Chopra,3 Noel Casey,4 Lee E. Goldstein,4 Stuart R. Hameroff,5 and Rudolph E. Tanzi6

  • wwwDOTdddmagDOTcom/news/2015/03/study-thousands-brains-reveals-tau-driver-alzheimers#at_pco=smlwn-1.0&at_si=55178af38988fc69&at_ab=per-2&at_pos=0&at_tot=1

  • Dr. Villemagne's paper explains it:

    "Objectives: The trial aimed to explore putative imaging markers to help inform future clinical trial design of PBT2 in Alzheimer’s disease (AD)".

    So it was a pilot study for imaging markers. It was not an efficacy study. As been told an efficacy study needs to have much bigger population to have enough power.

  • pivalde pivalde Mar 25, 2015 3:56 PM Flag

    cont....
    METHODS:

    Bioquin-HMPAO was labeled with 99mTc according to previous study. In accordance with the objectives of the study, animal model of AD created on healthy male Sprague Dawley rats with intrahippocampal stereotaxic injection of amyloid beta 1-42 (Aβ1-42). Intrahippocampal administration was applied to the CA1 area of hippocampus bilaterally (Aβ1-42 to the left side and PBS to the right side as control). Additionally, healthy male Sprague Dawley rats were utilized as naïve group. Twenty days after surgery, biodistribution studies of 99mTc-Bioquin-HMPAO on animal model of AD and control group were performed. Furthermore, saturation with Bioquin-7-carboxylic acid (Aβ targeting side of Bioquin-HMPAO) was applied for both experimental groups. Nissl staining for animal model of AD was performed. All animal experiments were carried out under the approval of the relevant Institutional Animal Review Committee of Ege University, (Number: 2010-155) İzmir, Turkey.

    RESULTS:

    Higher uptakes on hippocampus were observed at Aβ1-42 injected side in animal model of AD when compared with the control and naïve groups. Saturated studies with Bioquin-7-carboxylic acid compound showed that 99mTc labeled Bioquin-HMPAO compound has specificity on amyloid plaques (Figure 1).

    CONCLUSION:

    Consequences of the whole experimental studies, it is proposed that the radiolabeled compound (99mTc-Bioquin-HMPAO) might be improved and used as a novel brain amyloid plaque specific agent promising early diagnosis potential of AD.

  • Mol Imaging Radionucl Ther. 2015 Feb 5;24(1):40-1. doi: 10.4274/mirt.24.01.07.

    Investigation of 99mTc Labeled Clioquinol Derivative on Amyloid Plaque Specifity by Using Animal Model of Alzheimer's Disease.

    Yurt Kılcar A1, Biber Müftüler ZF, Evren V, Koylu EO, Kanıt L, Tekin V, Medine İE, Unak P.

    OBJECTIVE:

    Alzheimer's disease (AD), which comes up an important problem due to the aging population, has two hallmarks defined as amyloid plaques and neurofibrillary tangles. Despite the fact that AD affects a wide audience adversely, definitive diagnosis of AD still requires postmortem examination of the brain through histological staining of these hallmarks. Nowadays, these two hallmarks are playing crucial role in researches for diagnosis and treatment of AD. In addition, deficiency of AD diagnosis agents and limitation of assessing the blood-brain barrier (BBB) are main reasons of the current researches focusing on brain agents with plaque or tangle imaging potential. Metal-protein attenuating compounds (MPACs) such as clioquinol and cloxyquin have a great increasing promise on amyloid plaques. Yurt Kilcar et al. radiolabeled Bioquin-Hexa methyl propylene amine oxime (HMPAO) with 99mTc (99mTc-Bioquin-HMPAO) and evaluated the biodistribution on healthy male Balb/C mice (unpublished data). In current study, it is aimed to investigate amyloid plaque specifity of the 99mTc-Bioquin-HMPAO by using biodistribution studies on animal model of AD.

    METHODS:

    Bioquin-HMPAO was labeled with 99mTc according to previous study. In accordance with the objectives of the study, animal model of AD created on healthy male Sprague Dawley rats with intrahippocampal stereotaxic injection of amyloid beta 1-42 (Aβ1-42). Intrahippocampal administration was applied to the CA1 area of hippocampus bilaterally (Aβ1-42 to the left side and PBS to the right side as control). Additionally, healthy male Sprague Dawley rats were utilized as naïve group. Twe

  • pivalde pivalde Mar 24, 2015 11:45 AM Flag

    Victor Villemagne should have told it in his talk : reduced SUVR without brain swlling !!! Unfortunately his talk was before BIIB 037 talk.

  • pivalde pivalde Mar 24, 2015 9:53 AM Flag

    ITM, but there is a big but : PBT2 does the SUVR reduction without brain swelling !! Thanks ITM

  • Reply to

    BIIB 037 study SUVR 1.4, stll normal ?

    by pivalde Mar 22, 2015 10:51 AM
    pivalde pivalde Mar 22, 2015 1:17 PM Flag

    So to me it looks like the study was not done in MCI or early AD population but perhaps in age related memory loss population or in vascular dementia. I think this is a major design problem.

  • Reply to

    New Prana Scientist paper - CQ and Parkinsons

    by interestingtome Mar 22, 2015 11:47 AM
    pivalde pivalde Mar 22, 2015 12:28 PM Flag

    ITM, thanks again !!!

  • BiiB 037 study groups had their suvrs round 1.4 which is still normal according Masters. In the Imagine study suvrs were above 2.4. That was high but 1.4 level is very low.

  • Reply to

    BIogen AD Drug v. PBT2

    by interestingtome Mar 20, 2015 11:57 AM
    pivalde pivalde Mar 22, 2015 9:59 AM Flag

    ITM, thank you very much. The AF pictures explain perhaps more than Biogen wants. Why the 6mg arm was not ready when all others were ?? Was it started later ? but compared with the old placebo group or what ???

  • Reply to

    BIogen AD Drug v. PBT2

    by interestingtome Mar 20, 2015 11:57 AM
    pivalde pivalde Mar 20, 2015 4:46 PM Flag

    Hippocampus atrophy

  • Reply to

    BIogen AD Drug v. PBT2

    by interestingtome Mar 20, 2015 11:57 AM
    pivalde pivalde Mar 20, 2015 2:01 PM Flag

    This Biogen study is much bigger study than the Imagine study was with its 40 patients including 15 placebos. Placebo arm had 40 cases and all 3 treatment arms had over 30 cases. So it was easier to get statistically significant results if there would be differences. However it is also obvious that the drug had stronger effecacy than 250mg of PBT2 had in the Imagine study already at 3mg level.
    The problem will be the adverse effects and monthly i.v. injection of the drug. I would guess that there will be even more adverse effects during the second year, more so in the ApoE4 group and we know already that PBT2 did not cause major side effects during the 2y treatment.
    However I must agree with prof. Masters, this is a big step in demonstrating that abeta is bad. PBT2 also reduces abeta but it perhaps will take a longer treatment time or perhaps a bigger dosage than 250mg. Efficacy of 2y treatment will be seen soon. The animal studies support regeneration of neural tissues by PBT2, nothing like that has been demonstrated by amyloid antibodies.

  • pivalde pivalde Mar 19, 2015 4:37 PM Flag

    copper, we got 1y ago only main results and in July by Masters some further analyses of them. Now, i think, we will get some further analyses of the original Imagine study. Perhaps a bit better explanation why placebos responded as they did, perhaps something more interesting or just the same what is already known. IMO Victor will present something new, but everything relates the original 52 week Imagine study.

  • pivalde pivalde Mar 19, 2015 4:00 PM Flag

    So it looks like Victor Villemagne will report the imagine results. Most likely there will be some new results !!!

  • Reply to

    Colin Masters is speaking at ADPD tomorrow AM

    by interestingtome Mar 19, 2015 12:08 PM
    pivalde pivalde Mar 19, 2015 3:17 PM Flag

    ITM, could it be that he would present something like in Copenhagen last summer and add some more analyses done after his last talk ?? To my knowlege PBT2 is the only drug reducing amyloid so PBT2 needs to be one part of the talk unless there will be some Biogen news.

  • Reply to

    Anyone know the MOA of Biogen's AD drug?

    by esoteric687 Mar 19, 2015 1:14 PM
    pivalde pivalde Mar 19, 2015 2:02 PM Flag

    BIIB037 is human antiabeta antibody given i.v. 14 times during 52 weeks. The study is a safety, tolerability and pharmacokinetics study, looking the efficacy on PET scan as was the case with Babi and also with PBT2. The plan is to enrol 194 cases and get the results by June 2017. In this ph 1 study dosage is different in the different arms as low dosage, medium dosage and high dosage.

  • JAMA Neurol. 2015 Mar 16. doi: 10.1001/jamaneurol.2014.4821. [Epub ahead of print]

    Age, Sex, and APOE ε4 Effects on Memory, Brain Structure, and β-Amyloid Across the Adult Life Span.

    Jack CR Jr1, Wiste HJ2, Weigand SD2, Knopman DS3, Vemuri P1, Mielke MM2, Lowe V1, Senjem ML1, Gunter JL1, Machulda MM4, Gregg BE1, Pankratz VS2, Rocca WA5, Petersen RC3.

    Importance:

    Typical cognitive aging may be defined as age-associated changes in cognitive performance in individuals who remain free of dementia. Ideally, the full adult age spectrum should be included to assess brain imaging findings associated with typical aging.

    Objective:

    To compare age, sex, and APOE ε4 effects on memory, brain structure (adjusted hippocampal volume [HVa]), and amyloid positron emission tomography (PET) in cognitively normal individuals aged 30 to 95 years old.

    Design, Setting, and Participants:

    Cross-sectional observational study (March 2006 to October 2014) at an academic medical center. We studied 1246 cognitively normal individuals, including 1209 participants aged 50 to 95 years old enrolled in a population-based study of cognitive aging and 37 self-selected volunteers aged 30 to 49 years old.

    Main Outcomes and Measures:

    Memory, HVa, and amyloid PET.

    Results:

    Overall, memory worsened from age 30 years through the 90s. The HVa worsened gradually from age 30 years to the mid-60s and more steeply beyond that age. The median amyloid PET was low until age 70 years and increased thereafter. Memory was worse in men than in women overall (P 

  • This is a good sign !

PRAN
1.1399-0.0101(-0.88%)Mar 30 3:59 PMEDT