Alzheimer\'s Immunology Alzheimer\'s Disease (Ad)

Alzheimer's Immunology

Alzheimer's disease (AD) has become widely associated with aging since its "re-discovery" and accompanying research in the 1970s. In fact, AD is thought to affect over 25 million people worldwide (Lemere & Masliah, 2010). AD is diagnosed as a result of "progressive memory loss and a decline in cognitive abilities" (Lemere & Masliah, 2010). Many pathological conditions are thought to contribute to the onset and progression of AD, including: amyloid-? (a?) peptide extracellular plaques, tau protein aggregates from intracellular neurofibrillary tangles, gliosis, inflammation, neuritic dystrophy, neurotransmitter level changes, and overall neuron loss (Lemere & Masliah, 2010). Currently, there are no "disease-modifying therapies" available for the treatment of AD (Lemere & Masliah, 2010).

Research on AD and possible therapies has been abundant for decades. Other possible pathogenic causes involve metalloproteinases (MMP); some possible treatments include inhibition of "selective gamma-secretase inhibitors" for "lowering a? production," the use of generous amounts of curcumin (from curry) in cooking, or high intake of antioxidants such as Moringa oleifera (MO) (Stomrud & al, 2010; Basi & al, 2010; Schardt, 2007; Ganguly & al, 2005).

The most widely-discussed causes of AD involve amyloid-? (a?) peptide extracellular plaques and inflammation; past and current findings on these topics will be discussed further in the following sections.

Inflammation Hypothesis

Although the role of inflammation in AD development and progression has "emerged relatively recently," it is still linked to a buildup of proteins such as a? And tau (Zotova & al, 2010). However, as a result of research specifically on the role of inflammation, scientists have suggested the use of both anti-inflammatory drugs and immunization procedures against a? (Zotova & al, 2010).

The inflammation hypothesis was developed when "immune-related antigens and cells around amyloid plaques in the brains of patients" with AD were discovered (Zotova & al, 2010). This discovery was made in the 1980s and provided evidence that the human brain is not "immunologically isolated" (Zotova & al, 2010). Furthermore, studies from the 1990s found "activated complement factors" to neuroinflammation such as cytokines in the brains of AD patients (Zotova & al, 2010). Still, these inflammatory factors are considered to be the result of "amyloid within the CNS bringing about activation of microglia, initiating a pro-inflammatory cascade that results in the release of potentially neurotoxic substances, including cytokines, chemokines, reactive oxygen and nitrogen species, and various proteolytic enzymes, leading to degenerative changes in neurons. However, the exact role of inflammation in the pathology of AD and its mechanisms in terms of the cells involved - microglia, astrocytes and T. lymphocytes are still debated" (Zotova & al, 2010).

Other evidence in support of the inflammation hypothesis includes observations of a negative correlation between rheumatoid disease patients who are treated with anti-inflammatory drugs and the incidence of AD, miscellaneous studies showing a protective mechanism between anti-inflammatory treatments and the onset of AD, and human studies showing that NSAIDs may "reduce or prevent" AD (Zotova & al, 2010).

The Alzheimer's rat model (max 200 words)

McGill University scientists have developed genetically-mutated rats that develop "amyloid pathology" and can therefore model AD in humans (McGill University, 2010). This is important because rats are more intelligent than other animals studied such as mice, and therefore provide richer fodder for studying cognitive decline as a result of AD (McGill University, 2010). Studies so far show the transgenic rats exhibiting behaviors typical of AD, including progressive symptoms typical of different AD "stages" (McGill University, 2010). Specifically, these rats will allow researchers to study the possible existence of a "latent phase" in AD (McGill University, 2010).

The transgenic rat took researchers 10 years to develop by manipulating DNA with the addition of a gene which produces a? buildup after 6 to 7 months (McGill University, 2010). After 13 months, the rats begin to show signs of dementia including reduced cognitive ability and memory impairment (McGill University, 2010).

Amyloid B. immunotherapy

Past research

Past research on the effects of active or passive a? immunization on a? buildup and AD progression provided evidence that such immunization "protects against the progressive loss of synaptophysin in the hippocampal molecular layer and frontal neocortex of a transgenic mouse model of AD" (Buttini & al, 2005). This provided further support for the amyloid hypothesis.

Current research

Since the discovery of a? immunotherapy effectiveness in the treatment of AD in mice, the AN1792 a? vaccine was developed and tested on humans (Lemere & Masliah, 2010). Unfortunately, clinical trials were discontinued when around 6% of the subjects developed meningoencephalitis (Lemere & Masliah, 2010). However, since some subjects showed improvements in a? plaque clearance, several new a? immunotherapies have been developed and are currently undergoing clinical trials (Lemere & Masliah, 2010). Based on preliminary results from these clinical trials, scientists predict that a? immunotherapy will be most effective in "preventing or slowing the progression of AD when patients are immunized before or in the very earliest stages" of the onset of AD (Lemere & Masliah, 2010). Therefore, current research is also focused on identifying biomarkers to predict the "presymptomatic" stages of AD (Lemere & Masliah, 2010).