|March 25, 2004|
|Life Extension Update Exclusive |
New Alzheimer’s disease hypothesis
Alzheimer’s disease is one of several disease caused by protein misfolding. In some of these diseases mutations that cause misfolding have been identified, but with the exception of a rare form of familial Alzheimer’s disease, the cause in 95 percent of cases of the disease was unknown. This suggests a more common cause, and the Scripps researchers set out to find it.
In previous research, two of the current paper’s authors revealed how inflammation can lead to the formation of reactive oxygen species such as ozone, which can damage cholesterol and other molecules in the body. They found that during inflammation, ozone reacts with normal metabolites to produce toxic compounds, two of which they have labeled the "atheronals." They suggested that these compounds are involved in atherosclerosis because atheronals have been identified in atherosclerotic plaques removed from patients with the disease.
In the current study, Scripps research professor Jeffery W Kelly and colleagues examined the brains of autopsied patients with Alzheimer’s disease and compared them to normal brains, finding evidence of atheronals in both groups. The researchers believe that a precipitating event in the presence of atheronals, such as a the inflammation caused by a head injury, may propagate protein misfolding and the buildup of fibrils. The team also found that atheronals and lipid oxidation products accelerate the misfolding of amyloid beta in vitro.
Kelly and colleagues suggest that inflammation could create conditions in which cholesterol and fats react with ozone and other inflammatory compounds to produce abnormal metabolites, which modify the folding of amyloid beta protein, leading to misfolding of other unmodified amyloid beta proteins, which eventually results in Alzheimer's disease.
Dr Kelly commented, "If a certain inflammatory metabolite or family of metabolites confers risk later in life, then we need to know this, and we need to attack the problem.”
Inflammation is a protective response of the body that occurs during the process of repair. The four cardinal signs of inflammation are redness, swelling, heat, and pain. The Russian biologist Elie Metchnikoff proposed that the purpose of inflammation was to bring phagocytotic cells to the injured area in order to engulf invading bacteria. Both Metchnikoff and Paul Ehrlich (who developed the humoral theory of immunity) shared the Nobel Prize in 1908.
Alterations in blood flow occur with inflammation, primarily to increase local circulation and speed repair. The blood vessels become more permeable, which allows protein-rich fluid (exudate) to collect between cells. This excess extravascular fluid is called edema.
The mechanism of inflammation is a complex interaction of chemical messengers. Arachadonic acid, via 5-lipoxygenase, forms leukotrienes that cause vasoconstriction, bronchospasm (i.e., asthma), and increased permeability. Alternatively, arachadonic acid can form, via cyclooxygenase, prostaglandins, which have similar actions and cause pain. Aspirin and indomethican inhibit cyclooxygenase which results in pain relief, but does not address the underlying cause of the inflammation or stop the actions of the leukotrienes.
Inflammation can be acute, as occurs after a physical injury, or chronic. There are several causes of chronic inflammation, including:
Inflammation is considered to be an underlying cause of Alzheimer's disease, primarily because beta-amyloid is an inflammatory protein (Hull 1996; McGeer et al. 1999).
C-reactive protein is a marker of inflammation that is associated with Alzheimer's disease (Iwamoto et al. 1994).
It seems the aging brain is susceptible to inflammation from enzymes known as COX-2 (cyclo-oxygenase 2) and 5-LOX (5-lipoxygenase). To inhibit the actions of these destructive enzymes, Nexrutine ® and 5-Loxin extracts have been added to the new Cognitex formula.
Nexrutine ® , from a plant called Phellodendron amurense, inhibits the production of the inflammation causing COX-2 enzyme, without interfering with the beneficial enzyme COX-1 that plays a part in protecting the mucosal lining of the stomach.
5-Loxin is a derivative of b-boswellic acid, a resin from the Boswellia serrata tree. 5-Loxin acts as a specific inhibitor of the inflammatory agent 5-LOX. Newer research indicates that levels of 5-LOX increase with age and may trigger cell death in the brain.
Working synergistically, the combination of Nexrutine ® and 5-Loxin may provide maximum effectiveness through a dual inflammatory pathway blockade. In fact, a 5-LOX inhibitor such as 5-Loxin may actually improve the effectiveness of COX-2 inhibitors.
Since 1982 when Cognitex was introduced to Life Extension members, the formula has been modified several times reflecting the results of new studies to promote optimal health in the aging brain. The newest version of Cognitex includes nutrients to protect the brain from a wide range of age-related insults.
Pregnenolone is a natural hormone that decreases with age. It is considered the “mother hormone” because the body converts it into a variety of other important hormones such as estrogen, progesterone, testosterone, and DHEA. These hormones may be especially beneficial to the aging brain. The new Cognitex is available with or without pregnenolone. People with hormone-sensitive cancers should not take pregnenolone.
|Life Extension Magazine March 2004 issue |
Life Extension for the brain
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