Alterations in apoptotic signaling in lymphocytes of patients in early stage of Alzheimer's disease precede massive neuronal loss in the brain

• Autorzy: Wojsiat J. , Laskowska-Kaszub K. , Mandecka M. , Gabryelewicz T. , Kuznicki J. , Wojda U.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Alzheimer’s disease (AD) is the most common age-related dementia worldwide of unclear early pathogenesis. Mild Cognitive Impairment (MCI) represents an early AD stage, preceding massive deposition of Aβ aggregates and associated neuronal loss in the brain. Recently we demonstrated that sporadic AD (SAD) lymphoblasts show increased levels of p21 protein, the key regulator of G1/S cell cycle checkpoint and apoptosis (Bialopiotrowicz et al. 2011, Neurobiol Aging). In the current study we aimed to elucidate if p21 levels are altered early in AD, in lymphocytes of MCI patients, and to investigate the effects of p21 on the apoptotic response of SAD and MCI lymphocytes METHODS: We compared apoptotic response to 2 deoxy-D ribose (2dRib) in EBV-immortalized B-lymphoblasts from 16 patients with SAD, 17 patients with MCI and 10 age-matched healthy individuals without dementia. Apoptotic response was measured using flow cytometry assays: AnnexinV, mitochondrial membrane potential, and SubG1-phase. RESULTS: Comparing to controls, under basal conditions p21 levels assessed by immunoblotting were significantly elevated in MCI lymphoblasts, similarly as in SAD cells. 24 h after 2dRib treatment, apoptosis was higher in SAD cells than in controls, and after stimulation p21 decreased significantly in SAD and MCI cells. CONCLUSIONS: SAD lymphoblasts are significantly lessresistant to oxidative apoptotic stimuli than controls. In MCI lymphoblasts there were similar tendencies but without statistical significance. These results suggest that changes in the p21 levels and in apoptotic response in lymphocytes appear early in AD and gradually increase with the disease progression. Furthermore, our data indicate that lymphocytes may be useful for the development of new early AD diagnostic markers based on apoptotic regulatory proteins such as p21. This research was supported by the grant 2/BIOMARKAPD/ JPND/2012 and by the Nencki Institute statutory funds.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S36

Twórcy

autor

Wojsiat J.

• Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Laskowska-Kaszub K.

• Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Mandecka M.

• Alzheimer’s Disease Division, MSWiA Hospital in Warsaw, Warsaw, Poland

autor

Gabryelewicz T.

• Alzheimer’s Disease Division, MSWiA Hospital in Warsaw, Warsaw, Poland

autor

Kuznicki J.

• International Institute of Molecular and Cell Biology, Warsaw, Poland

autor

Wojda U.

• Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland