Statins Against Alzheimer’s Disease




Seahorse weeds

As the population ages, it is universally acknowledged that some will succumb to the awful fate of Alzheimer’s Disease (AD), a neurological disorder that accounts for 60-80% of all cases of dementia. Characterized by a decline in cognitive and social functions and severe memory loss, AD affects nearly 35% of the population over 85 years of age. Histopathologically, markers of AD include the formation of senile plaques, caused by the extracellular accumulation of amyloid fibrils in the brain, and intraneuronal aggregates of neurofibrillary tangles with lead to progressive brain dysfunction.

Recent figures indicate that as many as 35 million people worldwide have dementia, a value that is projected to almost double within the next two decades. Thus, it is no wonder that medical research is constantly trying to discover the most effective preventative measure to slow progression of the disease. Although the exact cause of AD remains elusive, several risk factors are hypothesized to be involved in its development, including high levels of plasma cholesterol. Indeed, accumulation of cholesterol has been associated with senile plaques and in transgenic models of AD. Taking into account the association between high plasma cholesterol and AD, Tramontine and colleagues recently conducted a study to explore the role of statins — a class of lipid-lowering drugs — in the protection against the disease. Although the positive effects of statins on cardiovascular diseases are well known, their potential neuroprotective effects demand further characterization.

The authors used the experimental intracerebroventricular (ICV) streptozotocin (STZ) animal model to demonstrate metabolic changes that are very similar to those found in the sporadic form of AD. In this model, deficits in learning, memory, and cognitive behavior have been reported. In addition, increased oxidative damage, alterations in glucose utilization and neuronal damage have been described. Molecularly, astrocytes play a fundamental role in glutamate metabolism by regulating extracellular levels of glutamate and intracellular levels of glutamine. They also participate in antioxidant defenses in the production of glutathione, coupled to glutamate metabolism. Changes in neurochemical parameters, such as glutamate uptake, glutamine synthetase activity, and glutathione have been investigated in the disease.

The authors administered 0.1 mL of pravastatin (5 mg/kg) to the animals every two days for four weeks. Serum biochemical measurements, hippocampal tissue samples, glutamine synthetase activity, glutathione levels, and glutamate uptake were examined. It was reported that glutathione content was reduced in the STZ-treated animals about 30% compared with the sham group, indicating the development of oxidative stress. However, administration of pravastatin was able to prevent the effect of STZ on glutathione content. Furthermore, pravastatin was able to prevent the observed decrease in hippocampal glutamine synthetase activity in the STZ treated animals. Finally, STZ-treated rats were found to have reduced total content of glutathione in there hippocampal slices, an effect that was reversed in animal models that were administered with pravastatin.

Glutatmatergic neurotransmission, gluatamate metabolism and antioxidant defense are strongly coupled in the neuroprotection against AD development. The current study suggests that pravastatin can interfere with these parameters by reversing some of the negative effects initiated by the disease. Hopefully with the increasing gains of medical research, future studies will also be able to demonstrate the contribution of statins in reducing cognitive impairment and brain damage in AD patients.

References

Maccioni RB, Muñoz JP, & Barbeito L (2001). The molecular bases of Alzheimer’s disease and other neurodegenerative disorders. Archives of medical research, 32 (5), 367-81 PMID: 11578751

Mori T, Paris D, Town T, Rojiani AM, Sparks DL, Delledonne A, Crawford F, Abdullah LI, Humphrey JA, Dickson DW, & Mullan MJ (2001). Cholesterol accumulates in senile plaques of Alzheimer disease patients and in transgenic APP(SW) mice. Journal of neuropathology and experimental neurology, 60 (8), 778-85 PMID: 11487052

Tramontina AC, Wartchow KM, Rodrigues L, Biasibetti R, Quincozes-Santos A, Bobermin L, Tramontina F, & Gonçalves CA (2011). The neuroprotective effect of two statins: simvastatin and pravastatin on a streptozotocin-induced model of Alzheimer’s disease in rats. Journal of neural transmission (Vienna, Austria : 1996), 118 (11), 1641-9 PMID: 21744242

Image via melissaf84 / Shutterstock.

  • James

    Of all the silliness this probably takes the cake. I thought we had progressed quite a bit beyond the backward cholesterol theory. Please take note it never once has been able to venture beyond the theory stage and even at that, highly speculative. AD and other neurological disorders are almost certainly caused by energy deficiency because of too much junk “food” at mitochondrial level, most likely an overabundance of oxidized N6 creating too much ROS and too much RNS. Please remove me from your e-mail list.

  • MML

    Still trying to find another use for statins. Has not the amyloid beta theory of alz been debunked. hyperphosphorylated tau is now considered of primary importance and statins cause tau to be hyperphosphorylated. did you not read about the incidence of cognitive dysfunction as a “side effect” of statins? Even the FDA web site now acknowledges this, along with an increased incidence of diabetes type 2. glucose metabolism, really? think interference with isoprenoid function is going to be useful in any disease state? statins will prove to be the biggest mistake in medical history.

  • Vanessa

    It seems that there is enough evidence from people taking statins that Alzheimer-type symptoms are actually CAUSED by statins, most likely due to the depletion of cholesterol in the brain which is necessary for correct cognitive function. A ridiculous article.

  • Pingback: Statins worsen brain function of Alzheimer’s sufferers | The GOLDEN RULE()

Amy Wong, MS

Amy Wong, MS, is a medical writer and conducts traumatic brain injury research in a large academic institution. She holds a Master’s of Science from the University of Toronto under the department of Pharmacology. Her studies pertained to the selective field of neuropsychopharmacology examining the biological implications of post-stroke depression.
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