Mark Thorson
2015-06-02 00:40:50 UTC
Here's the study which I find compelling evidence
that AD is not "type 3 diabetes". Insulin resistance
occurs, but glucose metabolism is not impaired.
The relevant discussion begins on page 17.
http://ibg.colorado.edu/pdf/Halter3_2012.pdf
Here's a study linking insulin signalling to tau
phosphorylation. It's a cell study, so admittedly a
thin reed on which to do more than idle speculation.
http://www.jbc.org/content/287/42/35222.full.pdf
Here's a study which makes a good case for the
intranasal route bypassing the blood-brain barrier
(BBB). In rodents, anyway.
http://www.neurosurgery.uthscsa.edu/journal_club/journals/JOURNAL%20ARTICLES/Scranton_2011_rostral_migratory.pdf
Older review of using intranasal insulin to cross
the BBB for treating AD.
http://www.biomedcentral.com/content/pdf/1471-2202-9-S3-S5.pdf
If this stuff is so good, when will we see some
big studies to nail down whether it really works?
If there's been a study like that, I must have
missed it. This appears to be the largest clinical
trial of intranasal insulin for AD to date:
http://www.kurvetech.com/pdf/an-intranasal-insulin-therapy-for-alzheimer-disease-9-2011.pdf
I'm not strong on statistics, so I wonder why
they use a delta-log scale to display their results,
rather than a linear scale. A scatter plot of their
individual data points would be even better. One
thing that raises an eyebrow is Figure 2A. Does the
effect disappear at the higher dose? The summary
of results in Table 2 seems to show the effects of
the treatment are very small, except in the case of
delayed story recall at the lower dose level.
Interesting that they saw no change in CSF tau
because that's the putative mechanism linking
insulin to AD, but they were evaluating tau using
a commercial tau antibody. I believe that's just
a gross measurement of tau -- it doesn't tell you
how much of that is hyperphosphorylated tau. It's
the conversion of tau to hyperphosphorylated tau
that is believed to be a critical step in the
disease process.
I have yet to see persuasive data to support
intranasal insulin as an effective treatment for AD,
but I certainly think more studies and perhaps
better study design are needed.
that AD is not "type 3 diabetes". Insulin resistance
occurs, but glucose metabolism is not impaired.
The relevant discussion begins on page 17.
http://ibg.colorado.edu/pdf/Halter3_2012.pdf
Here's a study linking insulin signalling to tau
phosphorylation. It's a cell study, so admittedly a
thin reed on which to do more than idle speculation.
http://www.jbc.org/content/287/42/35222.full.pdf
Here's a study which makes a good case for the
intranasal route bypassing the blood-brain barrier
(BBB). In rodents, anyway.
http://www.neurosurgery.uthscsa.edu/journal_club/journals/JOURNAL%20ARTICLES/Scranton_2011_rostral_migratory.pdf
Older review of using intranasal insulin to cross
the BBB for treating AD.
http://www.biomedcentral.com/content/pdf/1471-2202-9-S3-S5.pdf
If this stuff is so good, when will we see some
big studies to nail down whether it really works?
If there's been a study like that, I must have
missed it. This appears to be the largest clinical
trial of intranasal insulin for AD to date:
http://www.kurvetech.com/pdf/an-intranasal-insulin-therapy-for-alzheimer-disease-9-2011.pdf
I'm not strong on statistics, so I wonder why
they use a delta-log scale to display their results,
rather than a linear scale. A scatter plot of their
individual data points would be even better. One
thing that raises an eyebrow is Figure 2A. Does the
effect disappear at the higher dose? The summary
of results in Table 2 seems to show the effects of
the treatment are very small, except in the case of
delayed story recall at the lower dose level.
Interesting that they saw no change in CSF tau
because that's the putative mechanism linking
insulin to AD, but they were evaluating tau using
a commercial tau antibody. I believe that's just
a gross measurement of tau -- it doesn't tell you
how much of that is hyperphosphorylated tau. It's
the conversion of tau to hyperphosphorylated tau
that is believed to be a critical step in the
disease process.
I have yet to see persuasive data to support
intranasal insulin as an effective treatment for AD,
but I certainly think more studies and perhaps
better study design are needed.