Research Update | Ganoderma triterpenes delay cognitive decline caused by Alzheimer’s disease

A study published in "Oxidative Medicine and Cellular Longevity," conducted by the People's Hospital of Hunan Province (the First Affiliated Hospital of Hunan Normal University) and the Hunan Provincial Key Laboratory of Metabolomics for Critical and Severe Illnesses, indicates that ganoderic triterpenes can protect brain nerve cells and alleviate cognitive impairment caused by Alzheimer’s disease through mechanisms such as anti-apoptotic and antioxidant effects.

Ganoderma triterpenes slow down cognitive decline.

The researchers first used the total extract of ganoderma triterpenes ( Ganoderma lucidum Triterpenoids (abbreviated as GLTs) were administered to Alzheimer’s disease mice that had already exhibited early symptoms. Sixty days later, the mice’s cognitive abilities were assessed using a water maze test.

The so-called “water maze test” involves setting up a resting platform in a large, circular pool of water. Leveraging the mice’s natural aversion to water and their instinctive effort to find places to avoid it, researchers measure the time it takes for the mice to locate the platform and the distance they swim—these metrics serve as indicators of the mice’s cognitive abilities. If a mouse fails to find the resting platform after two continuous minutes, the researchers will guide the mouse to the platform’s location, helping it learn the task.

Although the starting point for each swim session varied, mice with normal brains were still able to quickly locate the resting platform through repeated daily experiences. The experiment was conducted over a total of 9 days, once per day. When the results from all sessions were averaged, it was found that Alzheimer’s disease mice (AD group) took twice as long and swam three-quarters farther than normal mice (normal control group) to find the resting platform, indicating a significant decline in cognitive function in the brain (Figures 1–2).

However, in Alzheimer’s disease mice that had been pre-treated with a high dose (1.4 g/kg per day) of Ganoderma lucidum triterpenes GLTs, the time required to find the resting platform and the swimming distance were nearly identical to those of normal mice, and also comparable to those of Alzheimer’s disease mice treated daily with donepezil—the standard clinical drug commonly used (the Western-medicine control group) (Figures 1–2).

Figure 1: Time required for mice to find the resting platform

(The less time required, the better the cognitive ability.)

Figure 2: Swimming distance of mice to find the resting platform.

(The shorter the required distance, the better the cognitive ability.)

The day after concluding the above experiment, the researchers removed the resting platform from the pool and then placed the mice back into the water for testing.

Thanks to their previous nine-day experience, the normal mice remembered the original location of the platform and therefore spent more time circling around nearby, searching for the “disappeared platform.” In contrast, the Alzheimer’s mice appeared somewhat disoriented and swam aimlessly without a clear sense of direction.

In contrast, Alzheimer’s mice protected by Ganoderma lucidum triterpenes (GLTs)—whether at a low dose (0.35 g/kg per day) or a high dose (1.4 g/kg per day)—showed behavior more similar to that of normal mice, and their efficacy was comparable to that of conventional Western medications (Figures 3–4).

Figure 3: Time spent by mice in the area where the platform was located.

(The longer the duration of stay, the better the cognitive ability.)

Figure 4: Proportion of the swimming trajectories of mice in the area where the platform was located.

(The higher the proportion, the better the cognitive ability.)

Ganoderma triterpenes help maintain the integrity of nerve cells.

Decline in learning and memory ability is the earliest cognitive impairment associated with Alzheimer’s disease. The neural cells responsible for this function are located in the hippocampus. Therefore, after completing the above-mentioned experiment, the researchers performed a further anatomical examination of the mice’s brains.

The results showed that in normal mice, the neurons in the hippocampus were neatly arranged, uniform in size, well-defined in shape, and exhibited clear distinctions between the cell membrane and the nucleus. In contrast, the neurons in the hippocampus of Alzheimer’s disease mice were disorganized, varied in size, irregular in shape, significantly reduced in number, and showed obvious structural damage.

However, this condition did not occur in Alzheimer’s disease mice fed with Ganoderma lucidum triterpenes (GLTs). Their hippocampal neurons remained highly intact, and no obvious signs of cell necrosis were observed, indicating that Ganoderma lucidum triterpenes exert a certain protective effect on the hippocampus (Figure 5).

Figure 5: Neuronal cells in the hippocampus of mice

Ganoderma triterpenes reduce neurofibrillary tangles.

At the same time, researchers also found that Alzheimer’s mice protected by ganoderma triterpenes had significantly fewer neurofibrillary tangles in the cerebral cortex (which stores long-term memory) and hippocampal tissue compared to untreated Alzheimer’s mice (Figure 6).

Figure 6: Neurofibrillary tangles in the hippocampus tissue of mice

Neurofibrillary tangles are one of the hallmark pathological features of Alzheimer’s disease. Unlike β-amyloid plaques, which accumulate outside cells, neurofibrillary tangles form inside nerve cells and are caused by mutations in the “tau protein.”

Under normal circumstances, tau protein binds to the cytoskeleton (i.e., microtubules), helping to form and stabilize the cytoskeleton. However, in the brains of Alzheimer's patients, tau protein undergoes mutations that prevent it from binding to the cytoskeleton.

As a result, this protein aggregates into clumps, forming so-called “neurofibrillary tangles” that accumulate in the cytoplasm and interfere with cellular function. Without tau protein, the cytoskeleton gradually becomes distorted, deformed, and eventually disintegrates, ultimately leading to cell death.

The number of neurofibrillary tangles reflects the severity of Alzheimer’s disease progression; therefore, ganoderic triterpenes, by inhibiting the formation of these tangles, likely represent one of the key mechanisms through which ganoderic triterpenes slow cognitive decline in Alzheimer’s disease.

Ganoderma triterpenes reduce neuronal apoptosis.

Whether it’s amyloid-beta plaques or neurofibrillary tangles, both drive nerve cells toward apoptosis. The more nerve cells die, the greater the loss of function, and the more severe the cognitive decline associated with Alzheimer’s disease becomes.

Analysis of hippocampal tissue from the experimental mice in each group revealed that the rate of neuronal cell death in Alzheimer’s disease mice was more than four times higher than that in age-matched normal mice. Although high-dose ganoderma triterpenes could not completely prevent abnormal neuronal apoptosis, they did manage to reduce the damage by half—and their efficacy was comparable to that of conventional Western medications (Figure 7).

Figure 7: Apoptosis rate of neuronal cells in the hippocampus of mice

Further analysis by the researchers revealed that in Alzheimer’s disease mice treated with ganoderma triterpenes, not only do the brain nerve cells exhibit a robust antioxidant mechanism capable of counteracting oxidative damage caused by beta-amyloid protein, but their apoptosis mechanisms are also less likely to be triggered.

In other words, ganoderic triterpenes enhance the stress resistance of brain nerve cells, enabling them to survive and function even in harsh environments.

Lingzhi polysaccharides also have effects.

The above research findings show that after ganoderic triterpenes enter the gastrointestinal tract via the esophagus, they can slow the progression of Alzheimer’s disease by exerting antioxidant, anti-apoptotic, and anti-neurofibrillary tangle effects.

A study jointly published in 2017 by Tongji University in Shanghai, the Chinese Academy of Sciences, and other institutions in “Stem Cell Reports” demonstrated that long-term consumption of Ganoderma lucidum water extracts or Ganoderma lucidum polysaccharides can reduce β-amyloid plaque deposition in the brains of Alzheimer’s disease model mice and slow down the rate of learning and memory decline. (For details, see: Ganoderma lucidum polysaccharides alleviate cognitive decline caused by Alzheimer's disease. )

Ganoderma triterpenes and polysaccharides appear to protect the Alzheimer’s-affected brain through different mechanisms. I wonder whether the combined effect of these two compounds might be even more effective in slowing down the progression of Alzheimer’s disease?

Once Alzheimer’s disease sets in, it’s often very difficult to reverse its progression. However, if we can manage to preserve even a little bit more of our cognitive functions—including learning and memory—during the limited time we have left, we might just be able to better cope with Alzheimer’s disease.

[Source of Information]

1. Yu N, et al. Ganoderma lucidum Triterpenoids (GLTs) Reduce Neuronal Apoptosis via Inhibition of ROCK Signal Pathway in APP/PS1 Transgenic Alzheimer's Disease Mice. Oxid Med Cell Longev. 2020; 2020: 9894037.

2. Huang S, et al. Polysaccharides from Ganoderma lucidum Promote Cognitive Function and Neural Progenitor Proliferation in a Mouse Model of Alzheimer's Disease. Stem Cell Reports. 2017;8(1):84-94.