14 Perspectives of Aptamers for Medical Applications
439
Other aptamer-base biomarkers for early diagnosis of the onset of CAD or target
therapy on heart attack and stroke are still within the preclinical discovery and safety
stage of development. Substantial additional work remains to be completed before
aptamer-based medicines can be safe from bench to the bedside in daily practice.
14.4.2.2 Neurodegeneration Disease
Neurodegenerative diseases are a heterogeneous group of disorders that are characterized by the progressive degeneration of the structure and function of the central
nervous system or peripheral nervous system. Common neurodegenerative diseases
include Alzheimer’s disease and Parkinson’s disease. In 2016, an estimated 5.4
million Americans were living with Alzheimer’s disease. By 2050, one new case
of Alzheimer’s is expected to develop every 33 s, resulting in nearly 1 million new
cases per year [219]. According to the 2020 report from Alzheimer’s Association,
Alzheimer’s disease is the sixth leading cause of death in the United States and the
fifth leading cause of death among Americans age 65 and older [220]. An estimated
930,000 people in the United States could be living with Parkinson’s disease by 2020
[221].
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by a progressive and irreversible cognitive decline. This disease occurs mainly
but not exclusively among elderly people. A number of young people were also
involved in this disease probably caused by environmental factors, genetic heritage,
or even behavior of routine life. A study from Norton et al. [222] suggested that
people can avoid AD by behavioral change. Early diagnosis and intervention will
delay the advance of AD.
The aggregation of the Amyloid-β (Aβ) is the hallmark of AD, and soluble
amyloid-β oligomers (AβOs), rather than Aβ fibrils or Aβ monomers, are the most
neurotoxic species involved in Alzheimer’s pathogenesis [223]. AβOs are derived
from the proteolytic cleavage of the amyloid precursor protein (APP) and obtained
from Aβ peptides with lengths of 40–42 amino acids [224]. AβOs can then form the
insoluble Aβ plaques that are the representative pathological feature of AD [225].
Ylera et al. firstly selected RNA aptamers against amyloid-β(1-40) (A-β40, named
β-55) in 2002 [226], which was verified to bind amyloid fibrils but not to A-β40
monomer. This aptamer specifically binds amyloid plaques in both ex vivo human
Alzheimer’s disease brain tissue and in vivo AD animal model. It presents the
potential to be an imaging probe for AD diagnosis [227].
T-SO508 is another DNA aptamer identified by Tsukakoshi et al. [228]. It can
bind to α-synuclein oligomers with a Kd of 68 nM and A-β40 oligomers with an
even better affinity (Kd of 25 nM). Zhu et al. [223] further developed this aptamer to
quantify Aβ oligomers with high selectivity and monitor the Aβ aggregation process.
Chan et al. [229] report a direct, inexpensive, and ultrasensitive aptamer-based
multiplex assay for the quantification of trace amounts of AD biomarkers in both
439
Other aptamer-base biomarkers for early diagnosis of the onset of CAD or target
therapy on heart attack and stroke are still within the preclinical discovery and safety
stage of development. Substantial additional work remains to be completed before
aptamer-based medicines can be safe from bench to the bedside in daily practice.
14.4.2.2 Neurodegeneration Disease
Neurodegenerative diseases are a heterogeneous group of disorders that are characterized by the progressive degeneration of the structure and function of the central
nervous system or peripheral nervous system. Common neurodegenerative diseases
include Alzheimer’s disease and Parkinson’s disease. In 2016, an estimated 5.4
million Americans were living with Alzheimer’s disease. By 2050, one new case
of Alzheimer’s is expected to develop every 33 s, resulting in nearly 1 million new
cases per year [219]. According to the 2020 report from Alzheimer’s Association,
Alzheimer’s disease is the sixth leading cause of death in the United States and the
fifth leading cause of death among Americans age 65 and older [220]. An estimated
930,000 people in the United States could be living with Parkinson’s disease by 2020
[221].
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by a progressive and irreversible cognitive decline. This disease occurs mainly
but not exclusively among elderly people. A number of young people were also
involved in this disease probably caused by environmental factors, genetic heritage,
or even behavior of routine life. A study from Norton et al. [222] suggested that
people can avoid AD by behavioral change. Early diagnosis and intervention will
delay the advance of AD.
The aggregation of the Amyloid-β (Aβ) is the hallmark of AD, and soluble
amyloid-β oligomers (AβOs), rather than Aβ fibrils or Aβ monomers, are the most
neurotoxic species involved in Alzheimer’s pathogenesis [223]. AβOs are derived
from the proteolytic cleavage of the amyloid precursor protein (APP) and obtained
from Aβ peptides with lengths of 40–42 amino acids [224]. AβOs can then form the
insoluble Aβ plaques that are the representative pathological feature of AD [225].
Ylera et al. firstly selected RNA aptamers against amyloid-β(1-40) (A-β40, named
β-55) in 2002 [226], which was verified to bind amyloid fibrils but not to A-β40
monomer. This aptamer specifically binds amyloid plaques in both ex vivo human
Alzheimer’s disease brain tissue and in vivo AD animal model. It presents the
potential to be an imaging probe for AD diagnosis [227].
T-SO508 is another DNA aptamer identified by Tsukakoshi et al. [228]. It can
bind to α-synuclein oligomers with a Kd of 68 nM and A-β40 oligomers with an
even better affinity (Kd of 25 nM). Zhu et al. [223] further developed this aptamer to
quantify Aβ oligomers with high selectivity and monitor the Aβ aggregation process.
Chan et al. [229] report a direct, inexpensive, and ultrasensitive aptamer-based
multiplex assay for the quantification of trace amounts of AD biomarkers in both