A criterion characterizing accumulated neurotoxicity of Aβ oligomers in Alzheimer's disease
Proceedings of the Royal Society A Mathematical Physical and Engineering Sciences,
Journal Year:
2025,
Volume and Issue:
481(2309)
Published: March 1, 2025
The
paper
develops
a
criterion
to
quantify
the
accumulated
neurotoxicity
of
extracellular
amyloid
beta
(Aβ)
oligomers
in
Alzheimer's
disease
(AD).
Accumulated
is
determined
by
integrating
concentration
Aβ
within
control
volume
(CV)
over
time.
In
scenario
low
rate
free
oligomer
deposition
into
senile
plaques
and
dysfunctional
degradation
machinery,
resulting
an
infinitely
long
half-life
monomers
aggregates,
obtained
analytical
solution
reveals
quadratic
relationship
between
This
suggests
that
initially,
increases
slowly
but
accelerates
as
time
progresses.
could
help
understand
prolonged
delay
onset
AD
symptoms.
Furthermore,
model
indicates
with
duration
aggregation
process,
it
implies
if
protein
system
compromised,
becomes
unavoidable.
Eventually,
neuronal
death
only
question
way
prevent
this
outcome
ensure
machinery
for
peptides
their
aggregates
remains
functional.
A
threshold
value
suggested.
developed
theory
exceeded,
nearby
neurons
will
die.
progression
analysed.
An
S-shaped
growth
pattern,
half-deposition
increases,
revealed.
addition,
sensitivity
different
parameter
values
examined.
Language: Английский
A criterion characterizing accumulated toxicity of Aβ oligomers in Alzheimer’s disease
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 20, 2024
Abstract
The
paper
develops
a
criterion
to
quantify
the
accumulated
neurotoxicity
of
Aβ
oligomers
in
Alzheimer’s
disease
(AD).
Accumulated
is
determined
by
integrating
concentration
within
control
volume
over
time.
In
scenario
low
rate
free
oligomer
deposition
into
senile
plaques
and
dysfunctional
degradation
machinery,
resulting
an
infinitely
long
half-life
monomers
aggregates,
obtained
analytical
solution
reveals
quadratic
relationship
between
This
suggests
that
initially,
increases
slowly
but
accelerates
as
time
progresses.
could
help
understand
prolonged
delay
onset
AD
symptoms.
Furthermore,
model
indicates
with
duration
aggregation
process,
it
implies
if
protein
system
compromised,
becomes
unavoidable.
Eventually,
neuronal
death
only
question
way
prevent
this
outcome
ensure
machinery
for
peptides
their
aggregates
remains
functional.
A
threshold
value
suggested.
developed
theory
exceeded,
nearby
neurons
will
die.
progression
analyzed.
An
S-shaped
growth
pattern
half-deposition
revealed.
Additionally,
sensitivity
different
parameter
values
examined.
Language: Английский
Effect of diffusivity of amyloid beta monomers on the formation of senile plaques
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Aug. 2, 2023
Abstract
Alzheimer’s
disease
(AD)
presents
a
perplexing
question:
why
does
its
development
span
decades,
even
though
individual
amyloid
beta
(Aβ)
deposits
(senile
plaques)
can
form
rapidly
in
as
little
24
hours,
recent
publications
suggest?
This
study
investigated
whether
the
formation
of
senile
plaques
be
limited
by
factors
other
than
polymerization
kinetics
alone.
Instead,
their
may
diffusion-driven
supply
Aβ
monomers,
along
with
rate
at
which
monomers
are
produced
from
precursor
protein
(APP)
and
undergo
degradation.
A
mathematical
model
incorporating
nucleation
autocatalytic
process
(via
Finke-Watzky
model),
well
monomer
diffusion,
was
proposed.
The
obtained
system
partial
differential
equations
solved
numerically,
simplified
version
analytically.
computational
results
predicted
that
it
takes
approximately
7
years
for
aggregates
to
reach
neurotoxic
concentration
50
μM.
Additionally,
sensitivity
analysis
performed
examine
how
diffusivity
production
impact
aggregates.
Language: Английский
Effect of diffusivity of amyloid beta monomers on the formation of senile plaques
Mathematical Medicine and Biology A Journal of the IMA,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 15, 2024
Abstract
Alzheimer’s
disease
(AD)
presents
a
perplexing
question:
why
does
its
development
span
decades,
even
though
individual
amyloid
beta
(Aβ)
deposits
(senile
plaques)
can
form
rapidly
in
as
little
24
hours,
recent
publications
suggest?
This
study
investigated
whether
the
formation
of
senile
plaques
be
limited
by
factors
other
than
polymerization
kinetics
alone.
Instead,
their
may
diffusion-driven
supply
Aβ
monomers,
along
with
rate
at
which
monomers
are
produced
from
precursor
protein
and
undergo
degradation.
A
mathematical
model
incorporating
nucleation
autocatalytic
process
(via
Finke–Watzky
model),
well
monomer
diffusion,
was
proposed.
The
obtained
system
partial
differential
equations
solved
numerically,
simplified
version
analytically.
computational
results
predicted
that
it
takes
approximately
7
years
for
aggregates
to
reach
neurotoxic
concentration
50
μM.
Additionally,
sensitivity
analysis
performed
examine
how
diffusivity
production
impact
aggregates.
Language: Английский
Efficacy and molecular mechanisms of hesperidin in mitigating Alzheimer's disease: A systematic review
European Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
283, P. 117144 - 117144
Published: Dec. 4, 2024
Language: Английский
Simulating the growth of TAF15 inclusions in neuron soma
Published: July 17, 2024
Abstract
To
the
best
of
author’s
knowledge,
this
paper
presents
first
attempt
to
develop
a
mathematical
model
formation
and
growth
inclusions
containing
misfolded
TATA-box
binding
protein
associated
factor
15
(TAF15).
It
has
recently
been
shown
that
TAF15
are
involved
in
approximately
10%
cases
frontotemporal
lobar
degeneration
(FTLD).
FTLD
is
second
most
common
neurodegenerative
disease
after
Alzheimer’s
(AD).
characterized
by
progressive
loss
personality,
behavioral
changes,
decline
language
skills
due
frontal
anterior
temporal
lobes.
The
simulates
monomer
production,
nucleation
autocatalytic
free
aggregates,
their
deposition
into
inclusions.
accuracy
numerical
solution
equations
validated
comparing
it
with
analytical
solutions
available
for
limiting
cases.
Physiologically
relevant
parameter
values
were
used
predict
inclusion
growth.
influenced
two
opposing
mechanisms:
rate
at
which
aggregates
deposited
production
from
monomers.
A
low
slows
growth,
while
high
hinders
new
thus
also
slowing
Consequently,
maximized
an
intermediate
Language: Английский
Simulating the Growth of TAF15 Inclusions in Neuron Soma
Journal of Biomechanical Engineering,
Journal Year:
2024,
Volume and Issue:
146(12)
Published: Sept. 2, 2024
To
the
best
of
author's
knowledge,
this
paper
presents
first
attempt
to
develop
a
mathematical
model
formation
and
growth
inclusions
containing
misfolded
TATA-box
binding
protein
associated
factor
15
(TAF15).
It
has
recently
been
shown
that
TAF15
are
involved
in
approximately
10%
cases
frontotemporal
lobar
degeneration
(FTLD).
FTLD
is
second
most
common
neurodegenerative
disease
after
Alzheimer's
(AD).
characterized
by
progressive
loss
personality,
behavioral
changes,
decline
language
skills
due
frontal
anterior
temporal
lobes.
The
simulates
monomer
production,
nucleation
autocatalytic
free
aggregates,
their
deposition
into
inclusions.
accuracy
numerical
solution
equations
validated
comparing
it
with
analytical
solutions
available
for
limiting
cases.
Physiologically
relevant
parameter
values
were
used
predict
inclusion
growth.
influenced
two
opposing
mechanisms:
rate
at
which
aggregates
deposited
production
from
monomers.
A
low
slows
growth,
while
high
hinders
new
thus
also
slowing
Consequently,
maximized
an
intermediate
Language: Английский