Using marine sources to extract DHA to treat Alzheimer's disease

Using marine sources to extract DHA to treat Alzheimer's disease

A recent one Marine drugs Journal study discusses the anti-neurodegenerative effects of docosahexaenoic acid (DHA) and DHA-rich phospholipids (DH-PL) derived from fishery and aquaculture byproducts, with a particular focus on how these components may help treat Alzheimer's disease (AD).

Learn: Marine sources of DHA-rich phospholipids with anti-Alzheimer effect.Photo credit: Mironov Vladimir / Shutterstock.com

What is DHA?

DHA is a long-chain omega-3 polyunsaturated fatty acid (PUFA) that is a fundamental structural component of the human brain, retina, cerebral cortex and skin. DHA is the most abundant omega-3 fatty acid in the gray matter of the brain and retina, accounting for approximately 30% and 90% of all n-3 PUFAs in the brain and retina, respectively.

The n-3 PUFAs are lipid components that can exist as triacylglycerols, phospholipids, free fatty acids (FFAs), and cholesterol esters (CEs). These PUFAs are categorized according to their number of carbon atoms and the number and position of unsaturated bonds. These compounds have crucial functions in the architecture of cell membranes, cholesterol transport and energy storage.

DHA plays an important role in supporting brain and eye development in newborns, as well as preventing premature births, tumors, some malignancies, inflammatory processes and cardiovascular diseases. The cardioprotective properties of DHA are attributed to its ability to alter lipid metabolism, vascular function and membrane dynamics, as well as its anti-inflammatory and antioxidant effects.

There are two ways to synthesize DHA, endogenously from alpha-linolenic acid (ALA) or exogenously from marine sources including fish oils, krill oils, mollusks or algae.

How does the human body synthesize DHA?

Endogenous DHA synthesis occurs primarily in the liver, which produces the enzymes elongase and desaturase. Within the endoplasmic reticulum (ER), Δ6-desaturase converts ALA to stearidonic acid, which is desaturated by 5-desaturase to produce eicosapentaenoic acid (EPA).

Low levels of DHA in the brain have been linked to various neurological disorders, including AD and Parkinson's disease. Therefore, it is imperative that n3-PUFAs be included in the human diet as endogenous synthesis is inefficient and decreases with age. Additionally, previous studies have suggested that increasing DHA consumption reduces the risk of AD and delays the onset of symptoms.

What is AD?

AD is a progressive, irreversible and complicated disease. Approximately 50 million people worldwide suffer from dementia, with AD accounting for 50-75% of these cases.

By 2050, the prevalence of dementia and AD is likely to double in Europe and triple worldwide, reaching up to 113 million people. It is generally believed that the onset of AD begins around age 20, long before symptoms appear.

A wide range of symptoms are associated with AD, including gradual memory loss, language difficulties, orientation problems, problems with visuospatial skills, behavioral problems, cholinergic function changes, inability to perform routine tasks, and end-stage dementia.

Pathogenesis of AD

AD arises due to the formation of extracellular peptides that produce β-amyloid plaques and tau neurofibrillary tangles (NFTs), both of which contribute to brain atrophy.

For example, β-amyloid plaques can disrupt interneuronal communication at synapses, thereby contributing to neurodegeneration that can lead to neuronal damage or death.

Conversely, abnormal chemical changes cause tau to detach from microtubules and form threads that eventually become tangled to form NFTs in neurons. These tangles block a neuron's transport system, impairing synaptic communication. In addition, the presence of toxic amyloid and tau-phosphorylated proteins leads to brain atrophy.

Causes of AD

AD is primarily caused by aging and genetics, with women more likely to develop the disease than men. Genetically, the presence of the ApoE-4 allele increases the likelihood of developing AD because these alleles contribute to the accumulation of the β-amyloid peptide.

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The development of AD can also be influenced by family factors, age and genetics. For example, the risk of developing AD increases in people with a first-degree relative who has the disease. AD symptoms can also be worsened by smoking, obesity and diabetes.

Adequate high-density lipoprotein cholesterol (HDL) levels optimize neurological function and are essential for synapse maintenance. Meanwhile, high cholesterol levels can increase the risk of AD.

Treatments for AD

There is a decrease in acetylcholine levels in the brains of AD patients, which can be attributed to an increased concentration of cholinesterases that break down acetylcholine in the brain.

Blocking these enzymes results in more acetylcholine being available for transfer between brain cells. Therefore, a cholinesterase inhibitor is the first-line treatment for AD and appears to effectively improve mild to moderate cognitive and functional symptoms.

Donepezil, rivastigmine, and galantamine all inhibit acetylcholinesterase; However, these medications are associated with various side effects such as dizziness, headaches, and confusion. Additionally, these remedies only provide temporary symptoms and pain relief. As a result, these drugs cannot be called disease modifiers and cannot reverse or delay the progression of AD.

The N-methyl-D-aspartate (NMDA) receptor antagonist protects against neurotoxicity by preventing the consequences of high glutamate levels. Memantine, a partial NMDA receptor antagonist, and its combination with donepezil, have been approved by the US Food and Drug Administration (FDA) for the treatment of moderate to severe AD.

Aducanumab, a novel drug with disease-modifying potential, is a monoclonal antibody that binds to β-amyloid amino acids, thereby reducing the production of β-amyloid plaques in the AD brain.

Natural, marine-derived DHA and AD

Biologically active marine chemicals exhibit chemical properties not found in terrestrial products. In general, phospholipids derived from marine species are recommended for use in the food, pharmaceutical and cosmetic industries due to their amphiphilic nature.

The structural diversity of neuroprotective marine chemicals includes polysaccharides, glycosaminoglycans, glycoproteins, lipids and glycolipids, and pigments. In addition, corals, sponges, algae, tunicates and marine bacteria are some marine organisms that produce secondary metabolites.

Fish consumption is also associated with a reduced incidence of AD. Various fish species, including mackerel, tuna and sardines, are rich in n-3 PUFAs, especially (DHA)

Mechanism of DHA in the treatment of AD

DHA-PL-rich diets stimulate acetylcholine release, restore cholinergic activity, maintain healthy PUFA levels, and prevent age-related hippocampal degeneration. In addition, DHA-PL may help inhibit tau phosphorylation, thereby reducing neuroinflammation.

The neuroprotective effects of DHA-enriched phosphatidylcholine (DHA-PC) and DHA-enriched phosphatidylserine (DHA-PS) were observed in aged rats with dementia. The hippocampus can be protected from oxidative stress and mitochondrial damage. Additionally, DHA-PS contributes to the development of insoluble β-amyloid in AD.

Marine sources of DHA

Salmon, chub mackerel, Atlantic herring, boarfish and sardines harbor excess DHA-PLs. It is important that the composition and concentration of DHA-PL vary depending on the growth environment, nutrition and stress on the organism. A rich source of bioactive chemicals is also found in the inedible parts of crustaceans.

Heads, blood, entrails, skin and tails are among the most important marine byproducts and contain high amounts of lipids, proteins, minerals and vitamins. Recently, marine byproducts have become one of the most sought-after sources of DHA-PLs as their use reduces potential waste generation and environmental supply concerns.

Various methods are available for the extraction of PLs, including organic solvents, atmospheric oxygen, high temperatures, and supercritical carbon dioxide (SC-CO2). SC-CO2 extraction is the most efficient method because it produces a higher quality product, is ecologically safe, has greater purity and yield, and has a shorter extraction time than other methods.

Reference:

• Ferreira, I., Rauter, AP, & Bandarra, NM (2022). Marine Quellen von DHA-reichen Phospholipiden mit Anti-Alzheimer-Effekt. Meeresdrogen. doi:10.3390/md20110662.

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