the Aβ42 K16N peptide was less harmful to neuroblastoma cells than wild-type Aβ42
the mutant Aβ peptide formed predominantly low-n oligomers in vitro
the mutant peptide was highly toxic when mixed in equimolar amounts with wild-type Aβ mixed with wild-type Aβ it aggregated into high-n oliogmers.
a) Aβ peptides carrying the Flemish mutation have relatively low aggregation propensity in vitro, including dimerization
b) Conformational changes are thought to explain the Flemish mutation's inhibitory effect on self-assembly and nucleation.
a) Arctic Aβ40 forms protofibrils at an increased propensity and faster rate compared with wild-type Aβ40
b) In Arctic AD brain differentially truncated abundant Aβ is deposited in plaques of variable numbers and shapes in different regions of the brain.
CAA caused by the Italian or Dutch Aβ variants is uniquely characterized by deposition of Aβ in the smooth muscle cells surrounding the cerebral vasculature
a) The discovery of this mutation was an early demonstration that a variant in the APP gene could cause severe amyloid deposition.
b) Extensive Aβ accumulates in the cerebral vessels, especially the meningeal arteries and the cerebro-cortical arterioles.
c) In vitro, this mutation accelerates Aβ aggregation, leading to increased fibril formation.
d) This mutation is associated with high levels of β-sheet conformation and induction of apoptosis in cerebral endothelial cells compared with wild-type Aβ
[K16N]Aβ42 was found to be less toxic than WT Aβ42 at equal concentrations. However, a mixture of the two adding up to the same concentration was equally or more toxic than WT Aβ42 alone
Fig.5. Oligomerization and toxicity of K16N substituted Aβ peptides.
(1) SH-SY5Y cells were incubated for 12 hours with either 2 μM freshly dissolved peptides (load) of Aβ40 (A) or Aβ42 (B), or oligomers (2–20x) obtained by SEC.
(2) Primary hippocampal neurons were incubated for 48 hours with 2 μM freshly dissolved peptides. Toxicity was determined by percentage of living cells compared to untreated control cells (n = 4–8). The data are presented as mean ± SEM. (*p < 0.001, **p < 0.0001). Reprinted with permission from Kaden et al .
It is characterized by high thermodynamic stability compared to other dimers, as well as the least tendency to enter into biochemical reactions to achieve equilibrium. As one of the biological consequences of finding a dimer with high thermodynamic stability, there is a low reactivity, a reduced rate of forming high-molecular complexes, including fibrils and oligomers.
It is characterized by reduced thermodynamic stability compared to other dimers, as well as the greatest tendency to enter into biochemical reactions to achieve equilibrium. As one of the biological consequences of the definition of a dimer with low thermodynamic stability is a high reactivity, an increased rate of formation of high-molecular complexes, including fibrils and oligomers.
Analysis of the stability of amyloid peptides taking into account hereditary mutations. The calculation was performed using the software developed by our team
Direct Correlation Results Between Numerical Values and Biological Effects