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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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ELISA scatter plots of Aβ42.Fractions of human brain homogenates from non-demented (ND), sporadic Alzheimer disease (SAD) and familial Alzheimer disease (FAD) were analyzed with an Aβ42-specific ELISA. Colored symbols each represents one case as listed in Figure 1 and horizontal lines indicate the mean value of each group. Data is expressed as nmol or pmol/g of protein. a) TBS-soluble Aβ42 in frontal cortex; b) TBS-soluble Aβ42 in occipital cortex; c) SDS-soluble Aβ42 in frontal cortex; d) SDS-soluble Aβ42 in occipital cortex; e) FA-soluble Aβ42 in frontal cortex; f) FA-soluble Aβ42 in occipital cortex; g) Total Aβ42 (TBS+SDS+FA) in frontal cortex; h) Total Aβ42 (TBS+SDS+FA) in occipital cortex *<0.05; **<0.01.
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pone-0055847-g003: ELISA scatter plots of Aβ42.Fractions of human brain homogenates from non-demented (ND), sporadic Alzheimer disease (SAD) and familial Alzheimer disease (FAD) were analyzed with an Aβ42-specific ELISA. Colored symbols each represents one case as listed in Figure 1 and horizontal lines indicate the mean value of each group. Data is expressed as nmol or pmol/g of protein. a) TBS-soluble Aβ42 in frontal cortex; b) TBS-soluble Aβ42 in occipital cortex; c) SDS-soluble Aβ42 in frontal cortex; d) SDS-soluble Aβ42 in occipital cortex; e) FA-soluble Aβ42 in frontal cortex; f) FA-soluble Aβ42 in occipital cortex; g) Total Aβ42 (TBS+SDS+FA) in frontal cortex; h) Total Aβ42 (TBS+SDS+FA) in occipital cortex *<0.05; **<0.01.

Mentions: Immunoassays for Aβ40, Aβ42 and Aβ43 were performed for each ND, SAD and FAD case and the amount of Aβ was calculated and expressed in nmol or pmol/g protein as shown in Fig. 2, 3 and 4 (mean group concentrations are listed in Table S1). One ND case was excluded from statistical analysis due to high Aβ levels and diffuse plaques, which indicated pre-symptomatic AD. However, this case is represented throughout the graphs as a green diamond.


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

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

ELISA scatter plots of Aβ42.Fractions of human brain homogenates from non-demented (ND), sporadic Alzheimer disease (SAD) and familial Alzheimer disease (FAD) were analyzed with an Aβ42-specific ELISA. Colored symbols each represents one case as listed in Figure 1 and horizontal lines indicate the mean value of each group. Data is expressed as nmol or pmol/g of protein. a) TBS-soluble Aβ42 in frontal cortex; b) TBS-soluble Aβ42 in occipital cortex; c) SDS-soluble Aβ42 in frontal cortex; d) SDS-soluble Aβ42 in occipital cortex; e) FA-soluble Aβ42 in frontal cortex; f) FA-soluble Aβ42 in occipital cortex; g) Total Aβ42 (TBS+SDS+FA) in frontal cortex; h) Total Aβ42 (TBS+SDS+FA) in occipital cortex *<0.05; **<0.01.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3569467&req=5

pone-0055847-g003: ELISA scatter plots of Aβ42.Fractions of human brain homogenates from non-demented (ND), sporadic Alzheimer disease (SAD) and familial Alzheimer disease (FAD) were analyzed with an Aβ42-specific ELISA. Colored symbols each represents one case as listed in Figure 1 and horizontal lines indicate the mean value of each group. Data is expressed as nmol or pmol/g of protein. a) TBS-soluble Aβ42 in frontal cortex; b) TBS-soluble Aβ42 in occipital cortex; c) SDS-soluble Aβ42 in frontal cortex; d) SDS-soluble Aβ42 in occipital cortex; e) FA-soluble Aβ42 in frontal cortex; f) FA-soluble Aβ42 in occipital cortex; g) Total Aβ42 (TBS+SDS+FA) in frontal cortex; h) Total Aβ42 (TBS+SDS+FA) in occipital cortex *<0.05; **<0.01.
Mentions: Immunoassays for Aβ40, Aβ42 and Aβ43 were performed for each ND, SAD and FAD case and the amount of Aβ was calculated and expressed in nmol or pmol/g protein as shown in Fig. 2, 3 and 4 (mean group concentrations are listed in Table S1). One ND case was excluded from statistical analysis due to high Aβ levels and diffuse plaques, which indicated pre-symptomatic AD. However, this case is represented throughout the graphs as a green diamond.

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