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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

Concentration of Dynamin1 in BA9 and BA24 tissues by ELISA from subjects with PDD, DLB, AD and controls.(A) BA9, (B) BA24, PDD: Parkinson’s Disease Dementia; DLB: Dementia with Lewy Body; AD: Alzheimer’s Disease. Bars represent mean and error bars SEM.
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f1: Concentration of Dynamin1 in BA9 and BA24 tissues by ELISA from subjects with PDD, DLB, AD and controls.(A) BA9, (B) BA24, PDD: Parkinson’s Disease Dementia; DLB: Dementia with Lewy Body; AD: Alzheimer’s Disease. Bars represent mean and error bars SEM.

Mentions: The results for protein expression in the prefrontal cortex, anterior cingulate and parietal cortex are shown inFigure 1,Figure 2, and inTable 2. Dynamin1 protein levels were not significantly different between groups (Kruskall-Wallis p=0.682 for BA9; p=0.120 for BA24,Figure 1 and dataset 3 for BA40). On the other hand, changes were found for the expression of CaMKII and the fraction of activated form, i.e. phospho-CaMKII (Table 2). Indeed, the phospho-/total CaMKII ratio was significantly lower in the AD group compared to control, PDD and DLB groups in the prefrontal cortex (one-way ANOVA F(3,115)=7.129, p<0.001;Figure 2). In the anterior cingulate cortex, this ratio was decreased in all three dementia groups compared to controls (Kruskall-Wallis χ2(3)=14.44, p=0.003;Figure 2). In the same brain region, although the level of Dynamin1 was decreased in the AD group, there was no significant difference between groups. In the parietal cortex, expression of phospho-CaMKII was significantly lower in PDD, DLB and AD compared to controls, with a stronger decrease in the AD group (Kruskall-Wallis χ2(3)=35.942, p<0.001;Table 2). The level of the ratio phospho-/total CaMKII in the DLB group was decreased compared to other groups (one-way ANOVA F(3,114)=3.45, p=0.019;Figure 2).


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)

Concentration of Dynamin1 in BA9 and BA24 tissues by ELISA from subjects with PDD, DLB, AD and controls.(A) BA9, (B) BA24, PDD: Parkinson’s Disease Dementia; DLB: Dementia with Lewy Body; AD: Alzheimer’s Disease. Bars represent mean and error bars SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Concentration of Dynamin1 in BA9 and BA24 tissues by ELISA from subjects with PDD, DLB, AD and controls.(A) BA9, (B) BA24, PDD: Parkinson’s Disease Dementia; DLB: Dementia with Lewy Body; AD: Alzheimer’s Disease. Bars represent mean and error bars SEM.
Mentions: The results for protein expression in the prefrontal cortex, anterior cingulate and parietal cortex are shown inFigure 1,Figure 2, and inTable 2. Dynamin1 protein levels were not significantly different between groups (Kruskall-Wallis p=0.682 for BA9; p=0.120 for BA24,Figure 1 and dataset 3 for BA40). On the other hand, changes were found for the expression of CaMKII and the fraction of activated form, i.e. phospho-CaMKII (Table 2). Indeed, the phospho-/total CaMKII ratio was significantly lower in the AD group compared to control, PDD and DLB groups in the prefrontal cortex (one-way ANOVA F(3,115)=7.129, p<0.001;Figure 2). In the anterior cingulate cortex, this ratio was decreased in all three dementia groups compared to controls (Kruskall-Wallis χ2(3)=14.44, p=0.003;Figure 2). In the same brain region, although the level of Dynamin1 was decreased in the AD group, there was no significant difference between groups. In the parietal cortex, expression of phospho-CaMKII was significantly lower in PDD, DLB and AD compared to controls, with a stronger decrease in the AD group (Kruskall-Wallis χ2(3)=35.942, p<0.001;Table 2). The level of the ratio phospho-/total CaMKII in the DLB group was decreased compared to other groups (one-way ANOVA F(3,114)=3.45, p=0.019;Figure 2).

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