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The pathogenic aβ43 is enriched in familial and sporadic Alzheimer disease.

Sandebring A, Welander H, Winblad B, Graff C, Tjernberg LO - PLoS ONE (2013)

Bottom Line: Levels of Aβ43, as well as Aβ40 and Aβ42, were quantified using ELISA.We compared quantitative data showing Aβ levels in occipital and frontal cortex from sporadic (SAD) and familial (FAD) AD cases, as well as non-demented (ND) controls.Results showed Aβ43 present in each fraction from the SAD and FAD cases, while its level was lower than the detection limit in the majority of the ND-cases.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, KI-Alzheimer's Disease Research center (KI-ADRC), Huddinge, Sweden.

ABSTRACT
The amyloid-cascade hypothesis posits that the role of amyloid β-peptide (Aβ) in Alzheimer disease (AD) involves polymerization into structures that eventually are deposited as amyloid plaques. During this process, neurotoxic oligomers are formed that induce synaptic loss and neuronal death. Several different isoforms of Aβ are produced, of which the 40 and 42 residue variants (Aβ40 and Aβ42) are the most common. Aβ42 has a strong tendency to form neurotoxic aggregates and is involved in AD pathogenesis. Longer Aβ isoforms, like the less studied Aβ43, are gaining attention for their higher propensity to aggregate into neurotoxic oligomers. To further investigate Aβ43 in AD, we conducted a quantitative study on Aβ43 levels in human brain. We homogenized human brain tissue and prepared fractions of various solubility; tris buffered saline (TBS), sodium dodecyl sulfate (SDS) and formic acid (FA). Levels of Aβ43, as well as Aβ40 and Aβ42, were quantified using ELISA. We compared quantitative data showing Aβ levels in occipital and frontal cortex from sporadic (SAD) and familial (FAD) AD cases, as well as non-demented (ND) controls. Results showed Aβ43 present in each fraction from the SAD and FAD cases, while its level was lower than the detection limit in the majority of the ND-cases. Aβ42 and Aβ43 were enriched in the less soluble fractions (SDS and FA) of SAD and FAD cases in both occipital and frontal cortex. Thus, although the total levels of Aβ43 in human brain are low compared to Aβ40 and Aβ42, we suggest that Aβ43 could initiate the formation of oligomers and amyloid plaques and thereby be crucial to AD pathogenesis.

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Related in: MedlinePlus

Aβ42/Aβ40 and Aβ43/Aβ40 ratios.a) Total Aβ42 level was divided by total Aβ40 level and by total Aβ43; b) Aβ43 total level was divided by total Aβ40 concentrations. *<0.05; **<0.01.
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pone-0055847-g006: Aβ42/Aβ40 and Aβ43/Aβ40 ratios.a) Total Aβ42 level was divided by total Aβ40 level and by total Aβ43; b) Aβ43 total level was divided by total Aβ40 concentrations. *<0.05; **<0.01.

Mentions: Calculating the ratios between Aβ isoforms is a popular way of presenting data about the different species. This is due to the fact that previous studies show the Aβ42/Aβ40 ratio is more highly correlated with AD than are the absolute levels of each Aβ isoform [36]. In order to explore the relation between Aβ40, Aβ42 and Aβ43, we calculated ratios between these peptides in all fractions from each individual case. The ratio between Aβ42 and Aβ40 was significantly greater in SAD compared to the ratios obtained for the ND group, in both frontal (Fig. 6a) and occipital cortex (Fig. 6b). Due to the high Aβ40 levels in the APPswe case the Aβ42/Aβ40 ratio was low. Consequently, the ratio for the FAD group was not significantly higher than for the ND group. However, both PSEN1 mutation carriers had highly elevated Aβ42/Aβ40 ratios. The ratio between Aβ43 and Aβ40 in frontal cortex of the SAD group was significantly increased compared to ND, suggesting the importance of Aβ43 for AD pathology. On the other hand, the Aβ43/40 ratio in the FAD group was significantly lower than that for the SAD group (Fig. 6c). This is partly due to the extremely high Aβ40 levels identified in the APPswe case. Also in occipital cortex, the Aβ43/40 ratio of the SAD group was significantly more increased than that of the ND group (Fig. 6d). Meanwhile, there was no mean ratio difference to the FAD group.


The pathogenic aβ43 is enriched in familial and sporadic Alzheimer disease.

Sandebring A, Welander H, Winblad B, Graff C, Tjernberg LO - PLoS ONE (2013)

Aβ42/Aβ40 and Aβ43/Aβ40 ratios.a) Total Aβ42 level was divided by total Aβ40 level and by total Aβ43; b) Aβ43 total level was divided by total Aβ40 concentrations. *<0.05; **<0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569467&req=5

pone-0055847-g006: Aβ42/Aβ40 and Aβ43/Aβ40 ratios.a) Total Aβ42 level was divided by total Aβ40 level and by total Aβ43; b) Aβ43 total level was divided by total Aβ40 concentrations. *<0.05; **<0.01.
Mentions: Calculating the ratios between Aβ isoforms is a popular way of presenting data about the different species. This is due to the fact that previous studies show the Aβ42/Aβ40 ratio is more highly correlated with AD than are the absolute levels of each Aβ isoform [36]. In order to explore the relation between Aβ40, Aβ42 and Aβ43, we calculated ratios between these peptides in all fractions from each individual case. The ratio between Aβ42 and Aβ40 was significantly greater in SAD compared to the ratios obtained for the ND group, in both frontal (Fig. 6a) and occipital cortex (Fig. 6b). Due to the high Aβ40 levels in the APPswe case the Aβ42/Aβ40 ratio was low. Consequently, the ratio for the FAD group was not significantly higher than for the ND group. However, both PSEN1 mutation carriers had highly elevated Aβ42/Aβ40 ratios. The ratio between Aβ43 and Aβ40 in frontal cortex of the SAD group was significantly increased compared to ND, suggesting the importance of Aβ43 for AD pathology. On the other hand, the Aβ43/40 ratio in the FAD group was significantly lower than that for the SAD group (Fig. 6c). This is partly due to the extremely high Aβ40 levels identified in the APPswe case. Also in occipital cortex, the Aβ43/40 ratio of the SAD group was significantly more increased than that of the ND group (Fig. 6d). Meanwhile, there was no mean ratio difference to the FAD group.

Bottom Line: Levels of Aβ43, as well as Aβ40 and Aβ42, were quantified using ELISA.We compared quantitative data showing Aβ levels in occipital and frontal cortex from sporadic (SAD) and familial (FAD) AD cases, as well as non-demented (ND) controls.Results showed Aβ43 present in each fraction from the SAD and FAD cases, while its level was lower than the detection limit in the majority of the ND-cases.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, KI-Alzheimer's Disease Research center (KI-ADRC), Huddinge, Sweden.

ABSTRACT
The amyloid-cascade hypothesis posits that the role of amyloid β-peptide (Aβ) in Alzheimer disease (AD) involves polymerization into structures that eventually are deposited as amyloid plaques. During this process, neurotoxic oligomers are formed that induce synaptic loss and neuronal death. Several different isoforms of Aβ are produced, of which the 40 and 42 residue variants (Aβ40 and Aβ42) are the most common. Aβ42 has a strong tendency to form neurotoxic aggregates and is involved in AD pathogenesis. Longer Aβ isoforms, like the less studied Aβ43, are gaining attention for their higher propensity to aggregate into neurotoxic oligomers. To further investigate Aβ43 in AD, we conducted a quantitative study on Aβ43 levels in human brain. We homogenized human brain tissue and prepared fractions of various solubility; tris buffered saline (TBS), sodium dodecyl sulfate (SDS) and formic acid (FA). Levels of Aβ43, as well as Aβ40 and Aβ42, were quantified using ELISA. We compared quantitative data showing Aβ levels in occipital and frontal cortex from sporadic (SAD) and familial (FAD) AD cases, as well as non-demented (ND) controls. Results showed Aβ43 present in each fraction from the SAD and FAD cases, while its level was lower than the detection limit in the majority of the ND-cases. Aβ42 and Aβ43 were enriched in the less soluble fractions (SDS and FA) of SAD and FAD cases in both occipital and frontal cortex. Thus, although the total levels of Aβ43 in human brain are low compared to Aβ40 and Aβ42, we suggest that Aβ43 could initiate the formation of oligomers and amyloid plaques and thereby be crucial to AD pathogenesis.

Show MeSH
Related in: MedlinePlus