title: Dynamin1 concentration in the prefrontal cortex is associated with cognitive impairment in Lewy body dementia.
abstract: Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD) together, represent the second most common cause of dementia, after Alzheimer's disease (AD). The synaptic dysfunctions underlying the cognitive decline and psychiatric symptoms observed throughout the development of PDD and DLB are still under investigation. In this study we examined the expression level of Dynamin1 and phospho-CaMKII, key proteins of endocytosis and synaptic plasticity respectively, as potential markers of molecular processes specifically deregulated with DLB and/or PDD. In order to measure the levels of these proteins, we isolated grey matter from post-mortem prefrontal cortex area (BA9), anterior cingulated gyrus (BA24) and parietal cortex (BA40) from DLB and PDD patients in comparison to age-matched controls and a group of AD cases. Clinical and pathological data available included the MMSE score, neuropsychiatric history, and semi-quantitative scores for AD pathology (plaques - tangles) and for α-synuclein (Lewy bodies). Changes in the expression of the synaptic markers, and correlates with neuropathological features and cognitive decline were predominantly found in the prefrontal cortex. On one hand, levels of Dynamin1 were significantly reduced, and correlated with a higher rate of cognitive decline observed in cases from three dementia groups. On the other hand, the fraction of phospho-CaMKII was decreased, and correlated with a high score of plaques and tangles in BA9. Interestingly, the correlation between the rate of cognitive decline and the level of Dynamin1 remained when the analysis was restricted to the PDD and DLB cases, highlighting an association of Dynamin1 with cognitive decline in people with Lewy Body dementia.
authors: Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, UK.
authors: Julie
authors: J
authors: Vallortigara
authors: Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, UK.
authors: Sindhoo
authors: S
authors: Rangarajan
authors: Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, UK.
authors: David
authors: D
authors: Whitfield
authors: Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, UK.
authors: Amani
authors: A
authors: Alghamdi
authors: Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, UK.
authors: David
authors: D
authors: Howlett
authors: Department of Neuropathology, Institute of Pathology, University of Debrecen, Debrecen, H-4032, Hungary.
authors: Tibor
authors: T
authors: Hortobágyi
authors: Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
authors: Mary
authors: M
authors: Johnson
authors: Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
authors: Johannes
authors: J
authors: Attems
authors: Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, UK.
authors: Clive
authors: C
authors: Ballard
authors: Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
authors: Alan
authors: A
authors: Thomas
authors: Department of Psychiatry, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0SP, UK.
authors: John
authors: J
authors: O'Brien
authors: Department of Neurobiology, Ward Sciences and Society, Karolinska Institute, Stockholm, SE-141, Sweden.
authors: Dag
authors: D
authors: Aarsland
authors: Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, UK.
authors: Paul
authors: P
authors: Francis
keywords: Alzheimer’s disease; Dementia with Lewy bodies; Parkinson’s disease with dementia; beta amyloid; cognitive impairment; synaptic dysfunction; synaptic plasticity; tau; vesicle recycling