1: CNS Drugs. 2003;17(1):27-45.

Links
The role of insulin resistance in the pathogenesis of
Alzheimer's disease: implications for treatment.
Watson GS, Craft S.
Geriatri !esear", #$uati%n, an$ C&inia& Center, 'eterans ())airs *uget
S%un$ +ea&t" Care S,ste-, Seatt&e, .as"ingt%n, /S(.
(n e-erging 0%$, %) e1i$ene suggests t"at an inrease$ 2re1a&ene %) insu&in
a0n%r-a&ities an$ insu&in resistane in (&3"ei-er4s $isease -a, %ntri0ute t%
t"e $isease 2at"%2",si%&%g, an$ &inia& s,-2t%-s. 5t "as &%ng 0een kn%6n
t"at insu&in is essentia& )%r energ, -eta0%&is- in t"e 2eri2"er,. 5n t"e 2ast 2
$ea$es, %n1ergent )in$ings "a1e 0egun t% $e-%nstrate t"at insu&in a&s% 2&a,s
a r%&e in energ, -eta0%&is- an$ %t"er as2ets %) CNS )unti%n. 5n1estigat%rs
re2%rte$ 20 ,ears ag% t"at insu&in an$ insu&in ree2t%rs 6ere $ense&, 0ut
se&eti1e&, e72resse$ in t"e 0rain, in&u$ing t"e -e$ia& te-2%ra& regi%ns t"at
su22%rt t"e )%r-ati%n %) -e-%r,. 5t "as reent&, 0een $e-%nstrate$ t"at
insu&in-sensiti1e g&u%se trans2%rters are &%a&ise$ t% t"e sa-e regi%ns
su22%rting -e-%r, an$ t"at insu&in 2&a,s a r%&e in -e-%r, )unti%ns.
C%&&eti1e&,, t"ese )in$ings suggest t"at insu&in -a, %ntri0ute t% n%r-a&
%gniti1e )unti%ning an$ t"at insu&in a0n%r-a&ities -a, e7aer0ate %gniti1e
i-2air-ents, su" as t"%se ass%iate$ 6it" (&3"ei-er4s $isease. 5nsu&in -a,
a&s% 2&a, a r%&e in regu&ating t"e a-,&%i$ 2reurs%r 2r%tein an$ its $eri1ati1e
0eta-a-,&%i$ ((0eta), 6"i" is ass%iate$ 6it" seni&e 2&a8ues, a
neur%2at"%&%gia& "a&&-ark %) (&3"ei-er4s $isease. 5t "as 0een 2r%2%se$ t"at
insu&in an ae&erate t"e intrae&&u&ar tra))iking %) (0eta an$ inter)ere 6it"
its $egra$ati%n. 9"ese )in$ings are %nsistent 6it" t"e n%ti%n t"at insu&in
a0n%r-a&ities -a, 2%tentia&&, in)&uene &e1e&s %) (0eta in t"e 0rains %)
2atients 6it" (&3"ei-er4s $isease. 9"e inrease$ %urrene %) insu&in
resistane in (&3"ei-er4s $isease an$ t"e nu-er%us -e"anis-s t"r%ug"
6"i" insu&in -a, a))et &inia& an$ 2at"%&%gia& as2ets %) t"e $isease
suggest t"at i-2r%1ing insu&in e))eti1eness -a, "a1e t"era2euti 0ene)it )%r
2atients 6it" (&3"ei-er4s $isease. 9"e t"ia3%&i$ine$i%ne r%sig&ita3%ne "as 0een
s"%6n t% "a1e a 2%tent insu&in-sensitising ati%n t"at a22ears t% 0e -e$iate$
t"r%ug" t"e 2er%7is%-e 2r%&i)erat%r-ati1ate$ ree2t%r-ga--a (**(!-
ga--a). **(!-ga--a ag%nists, su" as r%sig&ita3%ne, a&s% "a1e anti-
in)&a--at%r, e))ets t"at -a, 0e %) t"era2euti 0ene)it in 2atients 6it"
(&3"ei-er4s $isease. 9"is re1ie6 2resents e1i$ene suggesting t"at insu&in
resistane 2&a,s a r%&e in t"e 2at"%2",si%&%g, an$ &inia& s,-2t%-s %)
(&3"ei-er4s $isease. :ase$ %n t"is e1i$ene, 6e 2r%2%se t"at treat-ent %)
insu&in resistane -a, re$ue t"e risk %r retar$ t"e $e1e&%2-ent %)
(&3"ei-er4s $isease.