Asymmetric Dimethylarginine (ADMA) as a Bio-marker for Early-Stage Diagnostic of Cerebrovascular Diseases

Description:

Technology:  MUSC researchers have identified Asymmetric Dimethylarginine (ADMA) as a novel early-stage biomarker to diagnose brain vascular pathologies associated with Alzheimer’s disease (AD), vascular cognitive impairment and dementia (VCID), and multiple sclerosis (MS). Data gathered shows that Tg-SwDI mice, the most common model for AD-associated cerebral amyloid angiopathy (CAA), had age-dependent elevation of serum ADMA level comparing to wild type which was apparent as early as 8 months of age (figure 1).

To further demonstrate that ADMA is related to the diseases, the Tg-SwDI mice treated with addition ADMA showed aggravating spatial learning and memory performance. The deposition of Aβ40 and Aβ42 in the brain, plaque-like Aβ42 in the hippocampus and cortex are also observed (see published manuscript), indicating that the elevated ADMA level is associated with cerebrovascular diseases. 

Using a chemical-induced Experimental Autoimmune Encephalomyelitis (EAE) mice as the model for MS, the researcher also found out that the exogenous ADMA treatment increased the severity of EAE (Figure 2). In addition, the ADME treated mice showed a greater degree of neurodegeneration, proinflammatory markers, and reduction of anti-inflammatory markers (data not shown), indicating the correlation between ADMA and MS.

To further demonstrate the proof of concept, the researcher investigated the infiltration of vascular cells across the blood-brain barrier (BBB) in EAE mice with and without ADMA treatment. The morphological result on spinal lumbar showed that the cell infiltration in the brain area was increased in EAE mice and the level of infiltration aggravated after treating with ADMA (Figure 3).

In summary, the serum ADMA level is an early marker to diagnose the brain microvascular pathologies, including VCID, AD, and MS. Using ADMA as an indicator could help identify patients with the diseases before the irreversible symptoms present.

Overview: Alzheimer’s disease, cerebrovascular diseases, and multiple sclerosis, which could be induced by diabetes, hypertension, and hyperlipidemia are one of the most common neurologic pathologies with the therapeutics market expected to reach USD 12.43 Billion by 2026. The diagnostic of such neurological diseases usually relies on the early signs and symptoms, including memory impairment, changes in the personality of behaviors following by neuropsychological tests and brain-imaging tests. However, as the above symptoms show up, the neurological impairment has occurred. There is an unmet need for early diagnosis of neurological diseases. 

Applications: MS, stroke, dementia-related disorders, Alzheimer’s disease, and cerebrovascular diseases induced by hyperlipidemia, hypertension, diabetes. 

 

Advantages:  Early marker for brain vascular diseases diagnostic

 

Key Words: Asymmetric Dimethylarginine, Alzheimer’s disease, multiple sclerosis, autoimmune encephalomyelitis, cerebrovascular diseases, hyperlipidemia, hypertension, diabetes

 

Publication: Choi S et al.,  Regulation of endothelial barrier integrity by redox-dependent nitric oxide signaling: Implication in traumatic and inflammatory brain injuries. Nitric Oxide 2019, 83:51-64.

Choi S et al., Asymmetric dimethylarginine exacerbates cognitive dysfunction associated with cerebrovascular pathology. The FASEB Journal 2020, 00:1-16.

Inventors: Inderjit Singh, Avtar K. Singh       

Patent Status:       WO2020264516

MUSC-FRD Technology ID: P1988

 

Patent Information:
Category(s):
Therapeutic
For Information, Contact:
JuiTung (Ray ) Liu
PostDoc
MUSC Foundation for Research Development
liuju@musc.edu
Inventors:
Inderjit Singh
Avtar Singh
Keywords:
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