[ExI] The Dementia Plague

[Dave Sill]

On Tue, Oct 9, 2012 at 2:45 PM, Anders Sandberg <anders at aleph.se> wrote:

>  On 09/10/2012 14:09, Dave Sill wrote:
>
> <http://opinionator.blogs.nytimes.com/2012/09/25/bittman-is-alzheimers-type-3-diabetes/>
> *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*
>
>
> 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.
>

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.

>  *
> 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.
> *
>
>
> Evidence please. It is not a bad hypothesis, but it takes more than
> correlation to show anything.
>

http://www.ncbi.nlm.nih.gov/pubmed/16340083?dopt=Abstract

*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.*
*
*
http://www.ncbi.nlm.nih.gov/pubmed/15750215?dopt=Abstract

*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.*
*
*
http://www.ncbi.nlm.nih.gov/pubmed/15750214?dopt=Abstract

*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.*
*
*
-Dave
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://lists.extropy.org/pipermail/extropy-chat/attachments/20121009/a6daaf83/attachment.html>