On Tue, Oct 9, 2012 at 2:45 PM, Anders Sandberg <span dir="ltr"><<a href="mailto:anders@aleph.se" target="_blank">anders@aleph.se</a>></span> wrote:<br><div class="gmail_quote"><blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex">
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On 09/10/2012 14:09, Dave Sill wrote:
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<div><a href="http://opinionator.blogs.nytimes.com/2012/09/25/bittman-is-alzheimers-type-3-diabetes/" target="_blank"></a><i>The
idea that Alzheimer’s might be Type 3 diabetes has been around
since 2005, but the connection between poor diet and
Alzheimer’s is becoming more convincing</i></div>
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Note that this still does not merit the term "type 3 diabetes" - it
is a cringeworthy distortion of what we know, a bit like calling
ageing "AIDS type 2" (you do acquire immunodeficiency from it).
Nobody outside the popular press (of which New Scientist is part)
uses the term seriously.</div></blockquote><div> </div><div>I think that's an unfortunate bit of marketing but that doesn't make the underlying relationship less likely to be true. And nobody is saying this dietary connection between diabetes and Alzheimer's is settled...just that there may be something there worth investigating.</div>
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<div>What’s new is the thought that while diabetes doesn’t
“cause” Alzheimer’s, they have the same root: an over
consumption of those “foods” that mess with insulin’s many
roles.</div>
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Evidence please. It is not a bad hypothesis, but it takes more than
correlation to show anything. <br></div></blockquote><div><br></div><div><a href="http://www.ncbi.nlm.nih.gov/pubmed/16340083?dopt=Abstract">http://www.ncbi.nlm.nih.gov/pubmed/16340083?dopt=Abstract</a></div><div><br>
</div><div><i>Reduced glucose utilization and energy metabolism occur early in the course of Alzheimer's disease (AD) and correlate with impaired cognition. Glucose utilization and energy metabolism are regulated by insulin and insulin-like growth factor I (IGF-I), and correspondingly, studies have shown that cognitive impairment may be improved by glucose or insulin administration. Recently, we demonstrated significantly reduced levels of insulin and IGF-I polypeptide genes and their corresponding receptors in advanced AD relative to aged control brains. The abnormalities in gene expression were accompanied by impaired survival signaling downstream through PI3 kinase-Akt. The present work characterizes the abnormalities in insulin and IGF gene expression and receptor binding in brains with different Braak stage severities of AD. Realtime quantitative RT-PCR analysis of frontal lobe tissue demonstrated that increasing AD Braak Stage was associated with progressively reduced levels of mRNA corresponding to insulin, IGF-I, and IGF-II polypeptides and their receptors, tau, which is regulated by insulin and IGF-I, and the Hu D neuronal RNA binding protein. In contrast, progressively increased levels of amyloid beta protein precursor (AbetaPP), glial fibrillary acidic protein, and the IBA1/AIF1 microglial mRNA transcripts were detected with increasing AD Braak Stage. Impairments in growth factor and growth factor receptor expression and function were associated with increasing AD Braak stage dependent reductions in insulin, IGF-I, and IGF-II receptor binding, ATP levels, and choline acetyltransferase (ChAT) expression. Further studies demonstrated that: 1) ChAT expression increases with insulin or IGF-I stimulation; 2) ChAT is expressed in insulin and IGF-I receptor-positive cortical neurons; and 3) ChAT co-localization in insulin or IGF-I receptor-positive neurons is reduced in AD. Together, these data provide further evidence that AD represents a neuro-endocrine disorder that resembles a unique form of diabetes mellitus (? Type 3) and progresses with severity of neurodegeneration.</i></div>
<div><i><br></i></div><div><a href="http://www.ncbi.nlm.nih.gov/pubmed/15750215?dopt=Abstract">http://www.ncbi.nlm.nih.gov/pubmed/15750215?dopt=Abstract</a></div><div><br></div><div><i>The neurodegeneration that occurs in sporadic Alzheimer's disease (AD) is consistently associated with a number of characteristic histopathological, molecular, and biochemical abnormalities, including cell loss, abundant neurofibrillary tangles and dystrophic neurites, amyloid-beta deposits, increased activation of pro-death genes and signaling pathways, impaired energy metabolism/mitochondrial function, and evidence of chronic oxidative stress. The general inability to convincingly link these phenomena has resulted in the emergence and propagation of various heavily debated theories that focus on the role of one particular element in the pathogenesis of all other abnormalities. However, the accumulating evidence that reduced glucose utilization and deficient energy metabolism occur early in the course of disease, suggests a role for impaired insulin signaling in the pathogenesis of AD. The present work demonstrates extensive abnormalities in insulin and insulin-like growth factor type I and II (IGF-I and IGF-II) signaling mechanisms in brains with AD, and shows that while each of the corresponding growth factors is normally made in central nervous system (CNS) neurons, the expression levels are markedly reduced in AD. These abnormalities were associated with reduced levels of insulin receptor substrate (IRS) mRNA, tau mRNA, IRS-associated phosphotidylinositol 3-kinase, and phospho-Akt (activated), and increased glycogen synthase kinase-3beta activity and amyloid precursor protein mRNA expression. The strikingly reduced CNS expression of genes encoding insulin, IGF-I, and IGF-II, as well as the insulin and IGF-I receptors, suggests that AD may represent a neuro-endocrine disorder that resembles, yet is distinct from diabetes mellitus. Therefore, we propose the term, "Type 3 Diabetes" to reflect this newly identified pathogenic mechanism of neurodegeneration.</i></div>
<div><i><br></i></div><div><a href="http://www.ncbi.nlm.nih.gov/pubmed/15750214?dopt=Abstract">http://www.ncbi.nlm.nih.gov/pubmed/15750214?dopt=Abstract</a></div><div><br></div><div><i>Interest in characterizing the role of impaired insulin actions in Alzheimer's disease (AD) and vascular dementia is growing exponentially. This review details what is currently known about insulin, insulin-like growth factor type I (IGF-I) and IGF-II proteins and their corresponding receptors in the brain, and delineates the major controversies pertaining to alterations in the expression and function of these molecules in AD. The various experimental animal models generated by over-expression, mutation, or depletion of genes that are critical to the insulin or IGF signaling cascades are summarized, noting the degrees to which they reproduce the histopathological, biochemical, molecular, or behavioral abnormalities associated with AD. Although no single model was determined to be truly representative of AD, depletion of the neuronal insulin receptor and intracerebroventricular injection of Streptozotocin reproduce a number of important aspects of AD-type neurodegeneration, and therefore provide supportive evidence that AD may be caused in part by neuronal insulin resistance, i.e. brain diabetes. The extant literature did not resolve whether the CNS insulin resistance in AD represents a local disease process, or complication/extension of peripheral insulin resistance, i.e. chronic hyperglycemia, hyperinsulinemia, and Type 2 diabetes mellitus. The available epidemiological data are largely inconclusive with regard to the contribution of Type 2 diabetes mellitus to cognitive impairment and AD-type neurodegeneration. A major conclusion drawn from this review is that there is a genuine need for thorough and comprehensive study of the neuropathological changes associated with diabetes mellitus, in the presence or absence of superimposed AD or vascular dementia. Strategies for intervention may depend entirely upon whether the CNS disease processes are mediated by peripheral, central, or both types of insulin resistance.</i></div>
<div><i><br></i></div><div>-Dave</div><div><br></div></div>