| Abstract | Alzheimerova bolest (AB) je progresivni neurodegenerativni poremećaj, a neurobiološke promjene karakteristične za
AB nastupaju vrlo rano u odnosu na vrijeme ispoljavanja kliničkih simptoma. Blagi kognitivni poremećaj (engl. mild
cognitive impairment, MCI), u nekim slučajevima, može prethoditi AB-u. Ranije postavljanje dijagnoze, prije nastanka
značajnih kognitivnih deficita, te pravovremena terapijska intervencija, uvelike bi promijenili kvalitetu života i ishode
oboljelih. U tu se svrhu intenzivno istražuju novi biljezi i terapijske mete, poput moždanog neurotrofnog čimbenika
(engl. brain-derived neurotrophic factor, BDNF). Cilj ovog istraživanja bio je ispitati može li se razina ekspresije
BDNF-a (na razini gena i proteina) povezati sa stupnjem kognitivnog deficita, te istražiti povezanost dva najčešće
istraživana polimorfizma gena BDNF s dijagnozom AB-a, razinom kognitivnog oštećenja i utvrditi postoji li utjecaj
navedenih polimorfizama na ekspresiju gena BDNF ili na koncentraciju ovog neurotrofina na periferiji. U istraživanje
je bilo uključeno 153 ispitanika, podijeljenih prema dijagozi na ispitanike s AB-om i one s dijagnozom MCI-ja. Za
analizu su korišteni uzoci pune krvi iz koje je izvojena plazma siromašna trombocitima za određivanje koncentracije
BDNF-a, a frakcija s leukocitima korištena je za izolaciju ukupne RNA i DNA, odnosno određivanje ekspresije gena
BDNF i genotipizaciju polimorfizama gena BDNF rs6265 i rs56164415. Rezultati istraživanja upućuju na višu
koncentraciju BDNF-a u plazmi ispitanika oboljelih od AB-a u odnosu na ispitanike s MCI-jem, uz negativnu korelaciju
između koncentracije BDNF-a u plazmi i ostvarenog broja bodova na psihometrijskim testovima. Osim toga, zabilježena
je niža relativna ekspresija gena BDNF u ispitanika oboljelih od AB-a u odnosu na ispitanike s MCI-jem, što upućuje
na moguće kompenzatorne neuroprotektivne mehanizme. Promatranjem polimorfizama gena BDNF, zabilježena je viša
učestalost alela A, s obzirom na polimorfizam rs6265, u skupini ispitanika oboljelih od AB-a. Značajno bolje očuvane
kognitivne funkcije zabilježene su kod homozigota GG s obzirom na polimorfizam rs6265, odnosno kod nositelja alela
T u slučaju polimorfizma rs56164415, što upućuje na postojanje rizičnih alela za navedene polimorfizme i time daje
uvid u nasljednu komponentu bolesti. Dostupni podaci u literaturi su heterogeni i potrebna su daljnja istraživanja, s
naglaskom na uključivanje kontrolne skupine zdravih ispitanika usklađenih po dobi. |
| Abstract (english) | Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with characteristic neurobiological changes
appearing decades prior to symptom onset. In some cases, mild cognitive impairment (MCI) precedes AD. Earlier
diagnosis, before significant cognitive decline, would allow for earlier intervention and better quality of life for those
affected. Therefore, significant scientific effort is directed at the discovery of new biomarkers and therapeutic targets
for AD, such as brain-derived neurotrophic factor (BDNF). The aim of this study was to analyze whether there is a
connection between BDNF expression and cognitive decline, and whether the two most investigated BDNF
polymorphisms affect AD diagnosis, cognitive decline, BDNF expression or plasma BDNF concentration. A total of
153 participants were included in the study, divided into two subgroups according to diagnosis (AB or MCI). Whole
blood samples were processed in order to obtain platelet-poor plasma, which was used for the determination of BDNF
concentration. Genomic DNA and total RNA were isolated from peripheral blood for determining relative BDNF
expression and genotyping of BDNF polymorphisms rs6265 and rs56164415. Results suggest significantly increased
plasma BDNF concentration in AD patients compared to MCI subjects, while negative correlation was observed between
plasma BDNF concentration and psychometric test scores. Furthermore, lower BDNF gene expression was noticed in
patients with AD compared to MCI subjects. These findings might suggest compensatory neuroprotective mechanisms.
Regarding BDNF polymorphisms, a higher frequency of A allele (rs6265) was detected in AD patients, while rs6265
GG homozygotes and/or carriers of rs56164415 T allele performed better on psychometric tests. Identifying A and C
alleles as risk alleles gives us a better insight into genetic factors possibly affecting disease progression. Current
published data are heterogenous and further studies are needed, with an emphasis on inclusion of healthy age-matched
controls. |
