Intense research into the causes, treatment, and prevention of Alzheimer’s disease is underway right now throughout the world and medical studies on this disease are published daily. Below is an overview of some of the recent medical developments in Alzheimer’s disease research and treatments followed by links to websites with current news stories about developments in Alzheimer’s disease.

Pathogenesis

There is considerable disagreement among researchers over which of the two structural changes in the brain that characterize Alzheimer’s disease is the most important. Some believe that tau, the protein that is found in large amounts in an abnormal form in tangles, is the cause of neural cell death in Alzheimer’s disease while others believe that beta-amyloid, the protein that makes up the core of Alzheimer’s plaques is the main culprit.

Tau or beta-amyloid?

The emergence of tau as a possible cause of Alzheimer’s disease reflects a recent shift in the mainstream scientific sentiments about the disease. For many years, beta-amyloid was thought to be the only real candidate for the cause of Alzheimer’s disease. The reasoning for this included the fact that all the mutations that cause increased susceptibility to Alzheimer’s disease and the inherited form of the disease (familial Alzheimer’s disease) are in genes related to the beta-amyloid protein.

Mutations in the amyloid precursor protein (APP) cause familial Alzheimer’s disease and APP is a large protein found on the outer surface of neurons that, when cut, produces the beta-amyloid protein as a fragment. Presumably, the mutation that causes familial Alzheimer’s allows APP to be cut more easily, generating more beta-amyloid proteins that aggregate and form plaques leading to Alzheimer’s disease. The other two genes that cause familial Alzheimer’s disease, presenilin 1 and presenilin 2, are part of the molecular apparatus that is responsible for cutting APP and producing beta-amyloid. These mutations cause the production of beta-amyloid protein fragments that are especially likely to form plaques, thus leading to Alzheimer’s disease. However, there is no conclusive evidence that plaques themselves cause the disease or that they are more important than (or even that they appear in the brain before) the tau-containing tangles.

Tau is a protein that normally functions to hold in place central rod-like elements that give structure to the slender neural processes called axons. These central rods are called microtubules and their structure is critical to giving an axon its shape and to transporting materials like neurotransmitters to the tip of the axon where they can be released to signal other cells. When tau becomes abnormally phosphorylated, meaning it has more phosphate groups attached to it than normal, it can no longer hold the microtubules in their proper place and the whole structural assembly of the axon collapses. When this occurs, the abnormal tau proteins become sticky and end up associating with other tau proteins and tangles form. These tangles are always found in the brains of patients with Alzheimer’s disease.

Some recent evidence indicates that some people with early Alzheimer’s disease who die from other causes have tau protein tangles but no beta-amyloid plaques, suggesting that tau abnormalities can occur before beta-amyloid plaques form. Some researchers believe this means that the beta-amyloid plaques might not be the cause of Alzheimer’s disease at all and could instead be a response to other brain changes like abnormal tau. Some have even suggested that beta-amyloid plaques may actually be protective for neurons, acting like scar tissue and collecting beta-amyloid in one place so it can’t harm other neurons.

Even so, there is no conclusive evidence that tau is the cause of Alzheimer’s disease either. There may be yet another factor that precedes the development of both plaques and tangles that is yet to be discovered.

Inflammation

Regardless of whether is it tau tangles, beta-amyloid protein plaques, or some other factor that kills cells in Alzheimer’s disease, another process may be critical to the pathogenesis of Alzheimer’s. Inflammation, a normal response to infections, has been found in the brains of some people with Alzheimer’s disease and some researchers believe that it may be responsible for killing neurons. As beta-amyloid plaques develop in the spaces between neurons, cells of the immune system are at work attempting to clear away dead cells and the debris they leave behind. This is a normal process anywhere else in the body, but inflammation in the brain can cause more harm than good by releasing chemicals that may damage and ultimately kill neurons. Although researchers believe the inflammation occurs before plaques have fully formed, they aren’t sure how this relates to the disease process. There is also debate over the role of inflammation, with some researchers behind the idea that it has a damaging effect on neurons and others supporting the idea that inflammation may actually be beneficial because it helps clear away plaques.

Screening and diagnosis

One of the biggest problems with Alzheimer’s disease is that it currently can’t be diagnosed until symptoms have already begun to appear. Researchers are currently studying ways to diagnose the disease before the first symptoms show up. Moreover, the disease cannot be diagnosed for certain until brain tissue can be examined directly for the plaques and tangles characteristic of the disease, which requires a highly invasive brain biopsy or a postmortem examination. Several studies are underway to find better methods to confirm an Alzheimer’s diagnosis in living people.

Neuroimaging

A few recent studies have suggested that by using structural imaging it may be possible to detect subtle structural changes in the brains of people with Alzheimer’s disease before disease symptoms appear. The hippocampus, a region of the brain involved in memory that is normally affected by the plaques and tangles of Alzheimer’s disease, appears to shrink in some people who will later develop the symptoms of Alzheimer’s disease. While this is a promising finding, researchers need to figure out how to know for sure that hippocampus shrinkage is due to Alzheimer’s disease and not some other condition. Also, not everyone who develops Alzheimer’s disease shows this shrinkage before the onset of symptoms so this method would not be able to predict all Alzheimer’s cases.

Another area of research involves functional imaging, which measures the activity of brain cells in each region of the brain. One study used functional magnetic resonance imaging (fMRI) - which uses blood flow as a measure of neural activity - to examine the brains of people who are at risk for Alzheimer’s disease because they have relatives with the disease and/or they have the APOE-e4 gene. The study showed that these at-risk individuals had greater activity levels in areas of the brain involved with memory (including the hippocampus and portions of cerebral cortex) when they performed a memory task as compared to similarly aged people who were not high-risk. Another study using fMRI showed that some people who were not currently displaying any symptoms of Alzheimer’s disease also had increased activation in areas of the brain associated with memory function when performing memory tasks. Importantly, these people with the largest increases in brain activation were also the ones who performed the worst on a memory task given two years later. Both of these functional imaging studies suggest that high levels of activation in certain memory areas or the brain may be a predictor of future memory impairments.

Why would these people with no symptoms of Alzheimer’s disease show increased activity in regions of the brain involved in memory? Some scientists believe that what might be happening is individuals whose brains have started to lose cells due to the early process of Alzheimer’s disease may need to exert greater mental effort in these memory areas, or may recruit adjacent brain areas, to compensate for the lost function. Basically, these people have to work harder to complete the same task because they have less to work with. Perhaps these people can do this successfully for years without any signs of brain cell loss ever becoming apparent in their behavior. Eventually though, this catches up with them: too many neurons die and the extra effort or compensation is no longer sufficient to hide the memory deficits. At this point they start to show the symptoms of Alzheimer’s disease.

Another promising area of imaging research focuses on developing tracer compounds that could label the plaques and tangles that are the hallmarks of Alzheimer’s. Such a tracer could be injected and would attach to the tau or beta-amyloid proteins and make them visible in a brain image. One study showed that a tracer compound called Pittsburgh compound B can attach to beta-amyloid plaques and a subsequent positron emission tomography (PET) scan can detect their presence. If confirmed by further studies, this type of procedure might be used to detect plaques before symptoms of Alzheimer’s disease begin, or it could be used to confirm a diagnosis of Alzheimer’s disease in a living person.

Another recent functional imaging study attempted to diagnose Alzheimer’s disease by using PET scans that measured glucose use (which is a measure of the cells’ activity) in neurons of the hippocampus. Researchers found that this technique could correctly diagnose Alzheimer’s 94% of the time, even differentiating it from other types of dementia. This imaging technique also appeared to be able to identify people with only mild cognitive impairment, a sort of pre-Alzheimer’s condition. The specific level and pattern of reduced glucose use in the hippocampus was associated with different cognitive abilities: people with no impairment had normal levels of glucose use, while people with dementia had different patterns of reduced glucose use depending on whether they had Alzheimer’s disease or a different type of dementia. Lower glucose use by cells in the hippocampus suggests that the brain is not creating new memories as well as it should be. This technique will be studied further to determine if it can be used as a general diagnostic tool for Alzheimer’s disease.

There are many large scale studies underway right now to determine whether MRI and PET scans or other imaging techniques can be used to see the early brain changes of Alzheimer’s disease, to confirm an Alzheimer’s disease diagnosis, or to measure the disease’s progression.

Mild Cognitive Impairment

Recently, researchers have started investigating a condition called mild cognitive impairment (MCI) as a precursor to Alzheimer’s disease. MCI is a condition characterized by diminished mental capacity (especially memory) that is more serious than the changes that occur with normal aging but not serious enough to be considered Alzheimer’s disease. MCI has recently gotten attention as a transitional condition that can lead to Alzheimer’s disease: people with MCI are four times more likely to develop Alzheimer’s disease than those without it. However some people with MCI do not go on to develop Alzheimer’s disease and some may even revert back to normal cognitive ability.

Some studies have tried to determine if various interventions can decrease the likelihood that MCI will become Alzheimer’s disease. One study gave the cholinesterase inhibitor drug donepezil to a group of people with MCI and initially found that they were at reduced risk of progressing to Alzheimer’s disease when compared with their counterparts given a placebo (sugar pill). However, after three years, the rate of Alzheimer’s progression for the two groups was the same.

Hormone replacement therapy (HRT)

HRT is estrogen with or without added progesterone taken to improve the symptoms that occur when the onset of menopause causes levels of these hormones to decline rapidly. While some studies have suggested that HRT might reduce the risk of developing Alzheimer’s disease, a recent large scale study of HRT users indicated that there might actually be a small increase in Alzheimer’s disease risk from taking HRT. Obviously, more research is needed to determine what, if any, effect HRT has on Alzheimer’s disease risk.

Treatments

There are currently several new drugs under development for Alzheimer’s disease and there will be several more in the coming years. The prevalence of Alzheimer’s disease and the extremely high emotional and economic cost of caring for an Alzheimer’s disease patient create a lot of interest in and research money for Alzheimer’s disease treatments. Some of the recent treatments that have been investigated follow:

NSAIDs

There is some evidence that inflammation in the brain may contribute to the damage of Alzheimer’s disease. Some studies have suggested that drugs that reduce inflammation such as the nonsteroidal anti-inflammatory drugs (NSAIDs) including naproxen sodium and ibuprofen might help slow the progression of Alzheimer’s disease. Unfortunately, clinical trials conducted so far have not demonstrated any effect of taking these drugs after an Alzheimer’s disease diagnosis on disease progression. Research continues into these drugs and other anti-inflammatory compounds and their effect on Alzheimer’s disease progression.

Antioxidants

A study conducted years ago suggested that the antioxidant vitamin E could delay the progress of Alzheimer’s disease by several months. This sparked additional interest in other antioxidant compounds including vitamin C, selenium, alpha-lipoic acid, and coenzyme Q. These are all currently under study in patients with mild to moderate Alzheimer’s disease to determine if they can delay the progression of the disease.

Ginkgo biloba

Ginkgo biloba has gotten a lot of attention recently for its ability to improve brain circulation and memory. Researchers have also attempted to study the effects of this tree extract on Alzheimer’s disease patients. Some evidence suggests that it may help with the memory impairment of Alzheimer’s disease. Current studies are examining if ginkgo biloba can delay the cognitive declines of Alzheimer’s disease or perhaps prevent dementia from developing in older adults.

Estrogen

Estrogen, the primary female sex hormone may also protect neurons, according to several studies. Some researchers have explored whether this property could be used to help preserve neurons in people with Alzheimer’s disease. Clinical trials using estrogen in Alzheimer’s patients have not shown that estrogen can slow the progression of already diagnosed Alzheimer’s disease. One large scale study mentioned briefly above, found that estrogen given together with progesterone (as hormone replacement therapy) to otherwise healthy women actually increased the risk of Alzheimer’s disease in women over 65. More research is needed to find out how estrogen influences Alzheimer’s disease symptoms and if it can help reduce Alzheimer’s disease risk.

Prevention

Preventing Alzheimer’s disease from ever occurring would be the best possible outcome for everyone. Several researchers are investigating ways to delay or prevent the onset of Alzheimer’s and some of the recent results of these studies are discussed below:

Vaccines

Several years ago, a group of researchers developed a vaccine against Alzheimer’s that worked by breaking up deposits of beta-amyloid in the brain (plaques). The rationale behind this was that immunizing someone with the vaccine against beta-amyloid would allow the immune system to destroy plaques before they could contribute to neural cell death. Studies conducted in animals were so promising that human clinical trials were started. Unfortunately, some people experienced severe brain inflammation as a side effect of the vaccine so the trials had to be stopped. Despite this failure, scientists are still working on ways to develop a vaccine for Alzheimer’s disease.

NSAIDs

While studies of non steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen sodium in Alzheimer’s disease patients showed no effect on disease progression, several studies have shown that NSAIDs taken daily as a prophylactic measure may reduce the risk of developing Alzheimer’s. This may be because brain inflammation appears to play a role in Alzheimer’s disease pathogenesis and since these drugs reduce inflammation they may be able to help prevent the disease from developing. Researchers do not yet know what dose is optimal to prevent Alzheimer’s disease or whether everyone can benefit from NSAID use or just those people at high risk for Alzheimer’s. Thorough clinical trials need to be conducted to determine if people should take NSAIDs solely to prevent Alzheimer’s. NSAIDs can cause serious gastrointestinal bleeding, so talk to your doctor before taking them.

Statins

Statins are a class of drugs most often used to lower cholesterol levels in the blood. Examples of these drugs include simvastatin (Zocor) and atorvastatin (Lipitor). Recent studies have shown that they may also reduce the risk of Alzheimer’s disease, possibly by reducing the Alzheimer’s disease risk associated with high cholesterol. Research continues into these drugs and their effect on Alzheimer’s disease risk.

Belly shape

Researchers recently reported the results of a study that followed more than 6,000 people for 35 years. The study concluded that people with more abdominal fat (larger waist circumference) when they are in their 40’s were three times as likely to develop dementia (including Alzheimer’s disease) by the time they reach their 70’s as those with an average waist. It is currently unclear why having abdominal fat might increase the risk for dementia, but if you are have a large waist, losing weight (especially around the midsection) may help reduce your risk of Alzheimer’s disease.

Links to recent Alzheimer’s disease developments

Alzheimer’s disease news from the Alzheimer’s Association.
http://www.alz.org/news_and_events_in_the_news.asp

Alzheimer’s disease news on Science Daily, a digest of recent science research news.
http://www.sciencedaily.com/news/health_medicine/alzheimer’s/

Recent information on Alzheimer’s disease research from the National Institute on Aging.
http://www.nia.nih.gov/Alzheimers/ResearchInformation/NewsReleases/

Press releases about Alzheimer’s disease from the National Institute of Neurological Disorders and Stroke (NINDS).
http://www.ninds.nih.gov/disorders/alzheimersdisease/press_alzheimersdisease.htm

PubMed is a U.S. National Institutes of Health search engine that covers all research published in medical and bio-scientific journals.
http://www.ncbi.nlm.nih.gov/PubMed/

PubMed Central is the National Institutes of Health free digital archive of biomedical and life sciences journal literature.
http://www.pubmedcentral.nih.gov/

Medline Plus, a service of the NIH, has links to recent Alzheimer’s disease news stories.
http://www.nlm.nih.gov/medlineplus/alzheimersdisease.html#cat57

The U.S. Food and Drug Administration Center for Biologics Evaluation and Research is the government agency charged with reviewing and approving applications for new drugs and medical devices and their website ahs information about recent developments in these areas.
http://www.fda.gov/Cber/index.html

Information about clinical trials

If you are interested in finding out more about clinical trials for Alzheimer’s disease the National Institutes of Health has a clinical trials website at http://clinicaltrials.gov/.

To find a clinical trial being conducted in your area, visit the Healia Clinical Trials Search.