The most common form of dementia in the elderly – Alzheimer’s disease – is associated with amyloid plaques and Alzheimer’s fibrils. Both β-amyloid and p-tau are two pathogenic molecules that play a crucial role in the induction of the disease. It has now been shown that long-term treatment with Gingko biloba extract can significantly improve Alzheimer’s pathology.
Alzheimer’s dementia (AD) is a neurodegenerative disease in the course of which there is impairment of orientation, communication skills, autobiographical identity and alteration of personality traits. Neuropathological and neurochemical changes are characteristic, usually beginning insidiously and then developing slowly but steadily over a period of several years [1]. What exactly causes the degradation of nerve cells has not yet been fully elucidated. However, it is certain that the disease is pathologically characterized mainly by β-amyloid (Aβ) plaques and tau fibrils [2].
Aβ is a natural protein that arises from a precursor protein and is normally cleaved and degraded in the brain. As AD alters the degradation of amyloid precursor protein, increased Aβ-proteins are formed. These accumulate to form β-amyloid plaques, which are deposited between nerve cells and can no longer be broken down by the body [3]. Tau proteins are responsible for cell stability and nutrient supply. Chemical changes cause the protein to accumulate in the form of fibers – tau fibrils – in the nerve cell, causing them to lose their shape and function [3].
Key element detected?
Evidence suggests that oligomeric Aβ induces hyperphosphorylation and aggregation of tau and extends tau pathology from a limited region around the medial temporal cortex to the entire neocortex. Experiments have demonstrated that tau accumulation is associated with poorer cognitive performance and brain atrophy. In the cerebrospinal fluid of Alzheimer’s patients, the protein content of p-tau and the total amount of tau proteins are increased. How p-Tau affects the neuronal network is still unclear. However, different mechanisms are discussed:
- Hyperphosphorylation of tau disrupts the normal function of tau in stabilizing the cytoskeleton and regulating axonal transport
- Tau targets the tyrosine kinase Fyn and mediates Aβ-induced loss of the N-methyl-D-aspartate receptor at the postsynapse
- Tau accumulation dephosphorylates cAMP response element binding protein (CREB), thereby impairing synaptic junction formation
- p-Tau induces the accumulation of oligomeric insulin and insulin resistance in neurons
In any case, p-tau seems to be a key pathogenic molecule in AD and, accordingly, a reduction could halt the progression of the disease.
Autophagy – a pathway to lower p-tau levels?
There is growing evidence that macroautophagy may be an effective mechanism for reducing p-tau. In mice, p-tau was observed to accumulate in the brain when the major autophagic component (ATG7) was ablated in forebrain neurons. In addition, autophagy-promoting interventions lowered the protein level of cerebral p-tau. By enhancing neuronal autophagy via activation of chronic microglial inflammation, cerebral p-tau was reduced and cognitive deficit was attenuated [4]. Therefore, a study was conducted to investigate whether cerebral p-tau levels could be lowered by Ginkgo biloba extract EGb 761 and thus prevent AD pathogenesis. For this, human P301S tau mutant transgenic mice were fed EGb 761 added to the regular diet for two or five months.
Treatment with EGb 761 for five months was indeed able to significantly improve the cognitive function of the mice, attenuate the loss of synaptophysin, and restore the phosphorylation of CREB in the mouse brain. Also, the amount of p-tau protein was decreased and microglial pro-inflammatory activation was shifted to anti-inflammatory activation in the brain. However, this effect did not yet occur after the two-month therapy. Accordingly, long-term treatment with Ginkgo biloba extract EGb 761, a clinically available and well-tolerated herbal drug, improves Alzheimer’s pathology through mechanisms against multiple pathogenic processes of the disease.
Literature:
- https://neurotransconcept.com/indications/?i=DEM&p=2 (last accessed 08/17/2020)
- www.amboss.com/de/wissen/Morbus_Alzheimer (last accessed 08/17/2020)
- www.alzheimer-forschung.de/alzheimer/wasistalzheimer/veraenderungen-im-gehirn (last accessed 08/17/2020)
- Qin Y, Zhang Y, Tomic I, et al: Ginkgo biloba extract EGb 761 and Its Specific Components Elicit Protective Protein Clearance Through the Autophagy-Lysosomal Pathway in Tau-Transgenic Mice and Cultured Neurons. J Alzheimers Dis 2018; 65(1): 243-263.
InFo NEUROLOGY & PSYCHIATRY 2020; 18(5): 26.
