Naslov
Argyrophilic grain disease (Braak's dementia): an underestimated tauopathy and key to understanding Alzheimer's disease

Autori
Šimić, Goran

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, prošireni sažetak, ostalo

Izvornik
Neurologia Croatica 65 (Suppl. 2): 38 / - , 2016, 38-38

Skup
Hrvatski kongres o Alzheimerovoj bolesti CROCAD-16 s međunarodnim sudjelovanjem i Sastanak Mediteranske Alzheimer alijanse

Mjesto i datum
Tučepi, Hrvatska, 05.10.2016. - 08.10.2016

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
Argyrophilic grain disease (Braak's dementia) ; Alzheimer's disease ; tau protein ; post-translational modifications ; acetylation ; phosphorylation ; trans-synaptic spreading of tauopathy

Sažetak
Argyrophilic grain disease (AGD) is an adult-onset progressive dementia (also called Braak’s dementia) that is characterized by spindle-shaped argyrophilic grains found within neuronal processes. Argyrophilic grains are composed of tau protein isoforms with four repeat domains for microtubule binding (4R tau). In a study of 2661 non-selected brains at autopsy, AGD was found in 5% of individuals aged between 51 and 96 years. The finding that 6% of individuals from the same series had Alzheimer’s disease (AD) supports the view that AGD is an underestimated cause of dementia. Besides its frequent occurrence, AGD merits attention because it provides clues about the role of phosphorylation and acetylation for pathological changes of tau proteins. The investigation with the antibody recently developed to detect acetylation at Lys274 residue of tau has shown that acetylation of this epitope is a very early change in AD brains, which occurs even before tangles are detectable. Interestingly enough, acetylation of tau at Lys274 was detected in all tauopathies (both primary and secondary) as well as in mouse tauopathy model, except in AGD. Due to the fact that AGD pathological changes are confined to the medial part of the temporal lobe and lateral hypothalamus, it has been hypothesized that tau acetylation at Lys274 could promote trans-synaptic spreading of tau pathology in AD (whereas it could have a protective role in AGD in this respect). Finding that preventing acetylation of tau at Lys274 could decrease tau seeding and spreading capacity in AD warrants further investigations of tau acetylation as a potential new therapeutic target in AD, AGD, and other tauopathies.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Kliničke medicinske znanosti, Kognitivna znanost (prirodne, tehničke, biomedicina i zdravstvo, društvene i humanističke znanosti)

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