Naslov
"Amyloid cascade hypothesis for all" : fact or illusion?

Autori
Šalković-Petrišić, Melita ; Osmanović, Jelena ; Hoyer, Siegfried ; Riederer, Peter

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
4. hrvatski kongres o Alzheimerovoj bolesti ; u: Neurologia croatica 57 (2008) (S) / Šimić, Goran ; Mimica, Ninoslav - Zagreb, 2008, 72-73

Skup
Hrvatski kongres o Alzheimerovoj bolesti (4 ; 2008)

Mjesto i datum
Rovinj, Hrvatska, 08.10.2008. - 11.10.2008

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
sporadic Alzheimer disease; insulin; brain; insulin degrading enzyme; amyloid beta

Sažetak
The great majority of Alzheimer’s disease (AD) patients have sporadic type of disease (sAD) with age and several non-amyloid beta (Aβ)-related susceptibility genes as risk factors, suggesting that amyloid cascade hypothesis might not be true for sAD. Continuing our previous research, we have investigated whether damage to the brain insulin system in long-term could trigger Aβ pathology in streptozotocin-intracerebroventricular (STZ-icv) rats which have been proposed as an experimental model of sAD. Namely, although insulin resistant brain state and cognitive deficits have been developed as early as 1 month after the STZ-icv treatment, no signs of Aβ pathology could have been seen at that time-point. RT-PCR was used for measuring the expression of insulin (Ins-I), insulin receptor (IR) and insulin degrading enzyme (IDE) mRNA in hippocampus, while their respective protein expression was measured by immunoblotting, 3 and 6 months following the STZ-icv treatment. Immunohistochemistry and Congo red staining were used for Aβ pathology analysis. Cognitive deficits, measured by Morris Water Maze Test, were recorded during the whole 6 month-long observational period. Data were analyzed by Cruscal-Walles ANOVA and Mann-Whitney U test (P<0.05). In STZ-icv rats decreased hippocampal expression of Ins-I, IR and IDE mRNA was found both after 3 (85%, 19%, and 19%) and 6 (57%, 26%, and 38%) months, followed by decreased expression of IR (23% and 28%) and IDE (21% and 22%) protein, respectively. Development of Aβ pathology in STZ-icv treated rats was confirmed by finding of intracellular Aβ 1-42 aggregates after 3 months, and formation of primitive amyloid-like plaques after 6 months in cortical and hippocampal tissue. Data from studies on experimental, non-transgenic sAD animal model suggests that dysfunction in brain insulin system and IR signaling, found also in humans during aging and diabetes type II, might be the primary event capable of causing the development of Aβ neuroptahological AD hallmark on a long-term basis. Therefore, Aβ -related gene mutation should not be taken for granted as a trigger for other brain neurochemical alterations in sporadic AD form. Supported by Croatian MZOS (108-1080003-0020) and DAAD.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA