4. Discussion
The Ab peptide Ab1e40, and Ab1e42 to an even greater extent, is a
critical factor in triggering AD. The primary mechanisms of Ab
peptide-mediated action in the development of AD involve reactions
with metals, such as Cuþ or Fe2þ,19 or binding to receptors,
such as the N-methyl-D-aspartate (NMDA) receptor. Additionally,
after Ab enters the cell, it interferes with the electron transport
chain in mitochondria, leading to mitochondrial dysfunction and
the generation of excessive superoxide levels.20,21 In all these respects,
both Ab types could be classified as ROS inducers.
Plasma concentrations of both Ab1e40 and Ab1e42 increase with
age in individuals over the age of 65 years,22 in individuals who
carry mutations that cause early-onset familial AD,23 and in patients
with Down's syndrome, who are at heightened risk of
developing AD.24 Additionally, plasma Ab levels are elevated in first
degree relatives of people with AD, who are also at an increased risk
of developing the disease.25 The plasma concentrations of Ab1e40
and Ab1e42 were associated with risk and subtypes of dementia, a
prospective population-based cohort study of men and women
aged 55 y and older.24 High plasma concentrations of Ab1e40 were
associated with an increased risk of dementia, particularly in individuals
who have concomitantly low concentrations of Ab1e42;
these individuals had an over 10-fold increased risk of dementia
compared with individuals with low concentrations of both Ab1e40
and Ab1e42.26
In this study, we selected Ab1e40 as an inducer of neurotoxicity
in neuronal cells to investigate the relationship between CAE and
4. DiscussionThe Ab peptide Ab1e40, and Ab1e42 to an even greater extent, is acritical factor in triggering AD. The primary mechanisms of Abpeptide-mediated action in the development of AD involve reactionswith metals, such as Cuþ or Fe2þ,19 or binding to receptors,such as the N-methyl-D-aspartate (NMDA) receptor. Additionally,after Ab enters the cell, it interferes with the electron transportchain in mitochondria, leading to mitochondrial dysfunction andthe generation of excessive superoxide levels.20,21 In all these respects,both Ab types could be classified as ROS inducers.Plasma concentrations of both Ab1e40 and Ab1e42 increase withage in individuals over the age of 65 years,22 in individuals whocarry mutations that cause early-onset familial AD,23 and in patientswith Down's syndrome, who are at heightened risk ofdeveloping AD.24 Additionally, plasma Ab levels are elevated in firstdegree relatives of people with AD, who are also at an increased riskof developing the disease.25 The plasma concentrations of Ab1e40and Ab1e42 were associated with risk and subtypes of dementia, aprospective population-based cohort study of men and womenaged 55 y and older.24 High plasma concentrations of Ab1e40 wereassociated with an increased risk of dementia, particularly in individualswho have concomitantly low concentrations of Ab1e42;these individuals had an over 10-fold increased risk of dementiacompared with individuals with low concentrations of both Ab1e40
and Ab1e42.26
In this study, we selected Ab1e40 as an inducer of neurotoxicity
in neuronal cells to investigate the relationship between CAE and
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