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Advanced Neurology Antibodies as neurodegenerative biomarkers

involves less invasive procedures and the specimens
provide higher antibody concentrations. 93,94
4.1. Alzheimer’s disease

Reactive antibodies targeting the Aβ protein have been
extensively studied in AD as crucial players in the immune
response, Aβ accumulation, and disease prognosis. 65,66,95 A
decrease in antibody titles against Aβ has been described
in the sera from AD patients, 96-99 although binding to
specific peptides, Aβ 1-15 and Aβ 1-42 , seem to increase. 97,98
An increase in other antibodies has also been detected in
the serum of AD patients, 100-102 an observation potentially
relevant to the immune response. This line of evidence
102
corroborates their role as potential markers for disease
diagnosis and monitoring. Regarding tau protein, Figure 3. Summary of passive immunization therapies assessed in clinical
conflicting results have been reported. Lower levels of trials for neurodegenerative diseases.
reactive antibodies against tau were found in the serum
of AD patients compared with healthy individuals, 103,104 5. Reactive antibodies in passive
a trend that may vary depending on the patient’s sex. immunization
104
However, other studies found no significant differences In the realm of emerging therapies for approaching
in the levels of these antibodies between AD patients and neurodegenerative diseases, the development of monoclonal
groups with no cognitive impairment or mild cognitive antibodies designed for the recognition, binding, and
impairment. 105
elimination of pathological proteins, known as passive
4.2. Parkinson’s disease immunization, stands out as a potential strategy (Figure 3).
In AD, a spectrum of monoclonal antibodies has been
In the context of PD, divergent findings have been developed to target and remove Aβ protein, such as
observed regarding the levels of autoantibodies. In one set aducanumab, bapineuzumab, gantenerumab, solanezumab,
of studies, a significant increase in the levels of anti-α-syn and lecanemab. These antibodies exhibit variations in
119
antibodies was found in the serum of PD patients when their selectivity for polymorphic variants and their ability to
compared to control groups, 106-109 particularly in the early recognize specific Aβ epitopes. 120
stages of the disease. These findings could have relevant
implications, especially in the search for biomarkers Bapineuzumab, solanezumab, gantenerumab,
enabling early and accurate diagnosis of PD. 108,110 However, aducanumab, and lecanemab are humanized IgG1
further research is needed, as other studies have found no monoclonal antibodies targeting Aβ. Bapineuzumab
significant differences 111-113 or even a reduced level of these reacts to the N-terminal of the Aβ peptide, clearing
antibodies. 114 both fibrillar and soluble forms, although displaying a
higher affinity for amyloid plaques. Clinical studies
119
4.3. Amyotrophic lateral sclerosis suggest a reduction of Aβ levels in CSF along with an
In addition to AD and PD, reactive antibodies appear to improvement in some cognitive aspects. 121-123 However,
play a role in other neurodegenerative diseases, such as no significant differences in brain volume were found in
ALS. Elevated levels of autoantibodies were found in the treated patients, and adverse effects such as cerebral
124
serum of ALS patients 86,91,115,116 targeting different proteins edema were observed, 124-126 leading to the discontinuation
related to the pathogenesis of the disease, including TDP- of clinical trials. 127
43, β-actin, LRP4, and neurofilament. 116 Solanezumab binds to the middle domain of Aβ
115
91
86
119
In addition to their potential as serological biomarkers, and promotes the clearance of Aβ monomers. This
reactive antibodies are emerging as promising monoclonal antibody, considered a safe therapy, 128,129
candidates for therapeutic interventions in the field reduces Aβ levels in early stages, thereby slowing disease
of neurodegenerative diseases. These antibodies offer progression. 128-132 However, it did not demonstrate
a unique approach by harnessing the body’s immune significant improvement in cognitive functions or in the
system to attack and neutralize disease-associated brain patients’ ability to perform daily activities, raising questions
antigens. 117,118 about its effectiveness in AD. 130,133

Volume 3 Issue 1 (2024) 7 https://doi.org/10.36922/an.2058