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Dynamin1 concentration in the prefrontal cortex is associated with cognitive impairment in Lewy body dementia.

Vallortigara J, Rangarajan S, Whitfield D, Alghamdi A, Howlett D, Hortobágyi T, Johnson M, Attems J, Ballard C, Thomas A, O'Brien J, Aarsland D, Francis P - F1000Res (2014)

Bottom Line: Changes in the expression of the synaptic markers, and correlates with neuropathological features and cognitive decline were predominantly found in the prefrontal cortex.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.

View Article: PubMed Central - PubMed

Affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, UK.

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.

No MeSH data available.


Related in: MedlinePlus

Correlates between Dynamin1 level in BA9 and rate of cognitive decline.Correlation between values of Dynamin1 level in BA9 in dementia cases and the MMSE decline per year.
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f4: Correlates between Dynamin1 level in BA9 and rate of cognitive decline.Correlation between values of Dynamin1 level in BA9 in dementia cases and the MMSE decline per year.

Mentions: A significant association between MMSE decline per year and the level of Dynamin1 was observed in BA9, with a decrease in Dynamin1 level with the rate of cognitive decline (r=-0.280, p=0.019, n=70;Figure 4). This correlation is also significant when the analysis was restricted to the PDD and DLB cases (r=-0.327, p=0.014, n=56). In the same brain region, the ratio phospho/totalCaMKII was positively correlated to the MMSE scores before death (r=0.256, p=0.024, n=78), highlighting a decrease in the fraction of activated CaMKII protein with the cognitive deficit. However, when the AD group was excluded from the analysis, there was no correlation between phospho-CaMKII and MMSE.


Dynamin1 concentration in the prefrontal cortex is associated with cognitive impairment in Lewy body dementia.

Vallortigara J, Rangarajan S, Whitfield D, Alghamdi A, Howlett D, Hortobágyi T, Johnson M, Attems J, Ballard C, Thomas A, O'Brien J, Aarsland D, Francis P - F1000Res (2014)

Correlates between Dynamin1 level in BA9 and rate of cognitive decline.Correlation between values of Dynamin1 level in BA9 in dementia cases and the MMSE decline per year.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4309165&req=5

f4: Correlates between Dynamin1 level in BA9 and rate of cognitive decline.Correlation between values of Dynamin1 level in BA9 in dementia cases and the MMSE decline per year.
Mentions: A significant association between MMSE decline per year and the level of Dynamin1 was observed in BA9, with a decrease in Dynamin1 level with the rate of cognitive decline (r=-0.280, p=0.019, n=70;Figure 4). This correlation is also significant when the analysis was restricted to the PDD and DLB cases (r=-0.327, p=0.014, n=56). In the same brain region, the ratio phospho/totalCaMKII was positively correlated to the MMSE scores before death (r=0.256, p=0.024, n=78), highlighting a decrease in the fraction of activated CaMKII protein with the cognitive deficit. However, when the AD group was excluded from the analysis, there was no correlation between phospho-CaMKII and MMSE.

Bottom Line: Changes in the expression of the synaptic markers, and correlates with neuropathological features and cognitive decline were predominantly found in the prefrontal cortex.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.

View Article: PubMed Central - PubMed

Affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, UK.

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.

No MeSH data available.


Related in: MedlinePlus