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001-es BibID:	BIBFORM063678
Első szerző:	Vallortigara, Julie
Cím:	Decreased Levels of VAMP2 and Monomeric Alpha-Synuclein Correlate with Duration of Dementia / Julie Vallortigara, David Robert Edward Whitfield, William Quelch, Amani Alghamdi, David R. Howlett, Tibor Hortobágyi, Mary Johnson, Johannes Attems, John T. O'Brien, Alan J. Thomas, Clive G. Ballard, Dag Aarsland, Paul T. Francis
Dátum:	2015
ISSN:	1387-2877
Megjegyzések:	Alpha-synuclein (?-syn) aggregations are the key pathological hallmark of dementia withLewy bodies (DLB) and Parkinson's disease dementia (PDD), but are also frequently presentin Alzheimer's disease (AD). Yet much remains unknown about the role of ?-syn in thesynapse and the wider role of synaptic dysfunction in these dementias. Changes inconcentrations of key ♭SNAP (Soluble N-ethylmaleimide Sensitive Factor AttachmentProtein) Receptor' (SNARE) proteins as a consequence of alterations in the aggregation stateof ?-syn may contribute to synaptic dysfunction in patients with DLB, PDD and AD and resultin impaired cognition. We have studied a large cohort (n=130) of autopsy confirmed DLB,PDD, AD and control brains. Using semi-quantitative western blotting we havedemonstrated significant changes across the diagnostic groups of DLB, PDD and AD in theSNARE and vesicle proteins syntaxin, Munc18, VAMP2 and monomeric ?-syn in theprefrontal cortex, with a significant reduction of Munc18 in AD patients (p<0.001). Thiscorrelated to the final MMSE score before death (p=0.016). We also identified a significantnegative correlation between the duration of dementia and the levels of the bindingpartners VAMP2 (p=0.0004) and monomeric ?-syn (p=0.0002). It is of particular note that thisassociation was identified in people with AD. Our findings may indicate that an upregulationof SNARE complex related proteins occurs in the early stages of disease as an attempt atcompensating for failing synapses, prior to widespread deposition of pathological ?-syn.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Dementia with Lewy bodies Parkinson's disease dementia Alzheimer's disease Synaptic dysfunction SNARE process Alpha-synuclein VAMP2 Munc18
Megjelenés:	Journal Of Alzheimers Disease. - 50 : 1 (2015), p. 101-110. -
További szerzők:	Whitfield, David Quelch, William Alghamdi, Amani Howlett, David R. Hortobágyi Tibor (1965-) (patológus) Johnson, Mary Attems, Johannes O'Brien, John Thomas, Alan Ballard, Clive G. Aarsland, Dag Francis, Paul T.
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