Obesity and type 2 diabetes are associated with an increase in the
incidence and prevalence of Alzheimer's disease (AD) and an impaired cognitive
function. Because peripheral blood mononuclear cells (MNC) express amyloid
precursor protein (APP), the precursor of β-amyloid, which forms the
pathognomonic plaques in the brain, we hypothesized that APP expression
diminishes after the marked caloric restriction and weight loss associated with
Roux-en-Y gastric bypass (RYGB) surgery.Research Design and Methods:Fifteen type
2 diabetic patients with morbid obesity (body mass index, 52.1 ± 13 kg/m(2))
underwent RYGB, and the expression of inflammatory and AD-related genes was
examined before and after 6 months in plasma and in MNC.Results:Body mass index
fell to 40.4 ± 11.1 kg/m(2) at 6 months after RYGB. There was a significant fall
in plasma concentrations of glucose and insulin and in homeostasis model of
assessment for insulin resistance. The expression of APP mRNA fell by 31 ± 9%,
and that of protein fell by 36 ± 14%. In addition, there was a reduction in the
expression of other AD-related genes including presinilin-2, ADAM-9, GSK-3β,
PICALM, SORL-1, and clusterin (P < 0.05 for all). Additionally, the expression of
c-Fos, a subunit of the proinflammatory transcription factor AP-1, was also
suppressed after RYGB. These changes occurred in parallel with reductions in
other proinflammatory mediators including C-reactive protein and monocyte
chemoattractant protein-1.Conclusions:Thus, the reversal of the proinflammatory
state of obesity is associated with a concomitant reduction in the expression of
APP and other AD-related genes in MNC. We conclude that obesity and caloric
intake modulate the expression of APP in MNC. If indeed, this effect also occurs
in the brain, this may have implications for the pathogenesis and the treatment
of AD. It is relevant that cognitive function has been shown to improve with
weight loss following bariatric surgery.
1 comment:
That is NOT the only conclusion that one must come to. Suppose there is something in the GUT that is causing or exacerbating AD-type dementia. When the gut is cut out, that X factor leaves with it. It may have nothing to do with caloric intake. Perhaps Diabetes and Alzheimer's "takes guts" in a different sense.
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