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Spatial and temporal pattern of Ser199/Ser202/Thr205-phosphorylated tau expression in developing human brain and during Alzheimer's disease progression


Jovanov-Milošević, Nataša; Grbić, Kristina; Kostović, Ivica; Hof, Patrick; Šimić, Goran
Spatial and temporal pattern of Ser199/Ser202/Thr205-phosphorylated tau expression in developing human brain and during Alzheimer's disease progression // Neurol. Croat. Vol. 56 (Suppl. 2) / Ivkić, G ; Judaš, M ; Klarica, M ; Kostović, I ; Šimić, G ; Petanjek, Z (ur.).
Zagreb: Denona d.o.o., 2007. str. 132-133 (poster, domaća recenzija, sažetak, znanstveni)


Naslov
Spatial and temporal pattern of Ser199/Ser202/Thr205-phosphorylated tau expression in developing human brain and during Alzheimer's disease progression

Autori
Jovanov-Milošević, Nataša ; Grbić, Kristina ; Kostović, Ivica ; Hof, Patrick ; Šimić, Goran

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

Izvornik
Neurol. Croat. Vol. 56 (Suppl. 2) / Ivkić, G ; Judaš, M ; Klarica, M ; Kostović, I ; Šimić, G ; Petanjek, Z - Zagreb : Denona d.o.o., 2007, 132-133

Skup
The Second Croatian Congress of Neuroscience

Mjesto i datum
Zagreb, Hrvatska, 18-19.05.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
Tau protein; development; Alzheimer's disease; phosphorylation

Sažetak
Introduction: Some of our previous findings suggested that hyperphosphorylation of tau protein in Alzheimer's disease (AD) might result from the inapt reactivation of fetal plasticity mechanisms. Therefore, the aim of this study was to examine phosphorylation of tau protein, recognized by the AT8-immunoreactivity (AT8-ir) during several stages of fetal development, and to compare it with AT8-ir in normal elderly, mildly cognitively impaired (MCI) and AD brains. Material and Methods: The anti-human tau antibody AT8 was employed in indirect-immunocytochemistry and Western blot, on samples of fifteen fetal human brains - two adult control and two MCI, as well as ten AD cases. AT8 antibody reacts with tau only when multiple sites around Ser202, including Ser199, Ser202 and Thr205, are phosphorylated. Thus, AT8-ir is useful in detecting phosphorylation of Ser202/Thr205, a target epitope for proline-directed kinases. In addition, AT8-ir permits the evaluation of neuronal changes well before the actual formation of neurofibrillary tangles and neuropil threads. Results: Specific AT8-ir was found already at 10th week of gestation (w.g.), which was the earliest fetal stage examined. The most prominent AT8-ir was found in the lower subplate zone at about 18th w.g. and in the upper subplate around 20th w.g., then gradually diminished and disappeared completely to the end of 32nd w.g. During mid-gestation, the fornix as well as the subset of callosal commissural fibers was unambiguously AT8-ir, while the internal capsule remained unstained in this period. Although AT8-ir in fetal brain was distinct, we did not detect any AT8-ir structures in neuronal soma or dendrites. In comparison with control adult cases, many entorhinal and hippocampal neurons of MCI brains, as well as some neurons of the temporal isocortex, presented initial cytoskeletal changes such as AT8-ir tortuous varicose apical dendrites and curved, thickened dendrites. Beaded- or rod-like AT8-ir was most conspicuous in the perforant fascicle and CA1 axons projecting into the subiculum. In the AD brain AT8-immunoreactive neurons were characterized by coarse AT8-ir granules, but most tangle-bearing neurons were not AT8-ir. Conclusions: The present work provides data on the transient, zone- and fiber tract-specific tau phosphorylation during axonal outgrowth and elongation. Results obtained in MCI and AD cases clearly show a layer- and stage-specific pattern of tau hyperphosphorylation during the progression of Alzheimer's disease. Based on these findings we suggest that some proline-directed kinases are abnormally reactivated during the early course of AD.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti, Psihologija

Napomena
Časopis je indeksiran u Neuroscience Citation index i EMBASE/Excerpta Medica.



POVEZANOST RADA


Projekt / tema
108-1081870-1942 - Fosforilacija tau proteina u razvitku i Alzheimerovoj bolesti (Goran Šimić, )

Ustanove
Medicinski fakultet, Zagreb