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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 synaptic markers and AD neuropathological features.(A) ratio phospho/totalCaMKII level with plaques scores in BA9, (B) ratio phospho/totalCaMKII with plaques scores in BA9, (C) phosphoCaMKII with plaques scores in BA40 and (D) phosphoCaMKII with tangles scores in BA40. Scatter plots represent values and bars the mean for each group. º (p<0.05), ºº (p<0.01) and ººº (p<0.001).
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f3: Correlates between synaptic markers and AD neuropathological features.(A) ratio phospho/totalCaMKII level with plaques scores in BA9, (B) ratio phospho/totalCaMKII with plaques scores in BA9, (C) phosphoCaMKII with plaques scores in BA40 and (D) phosphoCaMKII with tangles scores in BA40. Scatter plots represent values and bars the mean for each group. º (p<0.05), ºº (p<0.01) and ººº (p<0.001).

Mentions: Figure 3 summarises the relationships found between synaptic markers and semi-quantitative scores of AD pathology in BA9 and BA40. The ratio phospho-/total CaMKII was decreased, with a high score of plaques (Kruskall-Wallis χ2(3)=8.549, p=0.036), and medium and high scores of tangles (one-way ANOVA F(3,111)=5.375, p=0.002) in BA9. On the other hand, phospho-CaMKII was significantly decreased with high scores of plaques and tangles in BA40 (one-way ANOVA F(3,111)=5.227, p=0.002 for plaques; one-way ANOVA F(3,112)=9.282, p<0.001 for tangles). There was no correlation between Dynamin1 concentration and neuropathological scores in BA9 or BA40 (one-way ANOVA, p>0.05, see data sets). No significant relationships were found between any neurochemical variable and pathological features in the anterior cingulate cortex (one-way ANOVA, p>0.05, see data sets).


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 synaptic markers and AD neuropathological features.(A) ratio phospho/totalCaMKII level with plaques scores in BA9, (B) ratio phospho/totalCaMKII with plaques scores in BA9, (C) phosphoCaMKII with plaques scores in BA40 and (D) phosphoCaMKII with tangles scores in BA40. Scatter plots represent values and bars the mean for each group. º (p<0.05), ºº (p<0.01) and ººº (p<0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Correlates between synaptic markers and AD neuropathological features.(A) ratio phospho/totalCaMKII level with plaques scores in BA9, (B) ratio phospho/totalCaMKII with plaques scores in BA9, (C) phosphoCaMKII with plaques scores in BA40 and (D) phosphoCaMKII with tangles scores in BA40. Scatter plots represent values and bars the mean for each group. º (p<0.05), ºº (p<0.01) and ººº (p<0.001).
Mentions: Figure 3 summarises the relationships found between synaptic markers and semi-quantitative scores of AD pathology in BA9 and BA40. The ratio phospho-/total CaMKII was decreased, with a high score of plaques (Kruskall-Wallis χ2(3)=8.549, p=0.036), and medium and high scores of tangles (one-way ANOVA F(3,111)=5.375, p=0.002) in BA9. On the other hand, phospho-CaMKII was significantly decreased with high scores of plaques and tangles in BA40 (one-way ANOVA F(3,111)=5.227, p=0.002 for plaques; one-way ANOVA F(3,112)=9.282, p<0.001 for tangles). There was no correlation between Dynamin1 concentration and neuropathological scores in BA9 or BA40 (one-way ANOVA, p>0.05, see data sets). No significant relationships were found between any neurochemical variable and pathological features in the anterior cingulate cortex (one-way ANOVA, p>0.05, see data sets).

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