Alzheimers Disease

What is Alzheimers Disease? Alzheimers Disease is an age-related degenerative brain disorder characterized by the abnormal accumulation of extracellular deposits called Amyloid Plaques and intraneuronal tangles of fibrils in the brain. These changes lead to neuronal atrophy and synapse loss in the medial temporal lobe limbic structures that are critical for short term memory and extend to the association cortices of the frontal, temporal, and parietal lobes as the disease progresses. (Braak and Braak, 1991). It is the leading cause of dementia, a pattern mental decline characterized by impairment in memory and at least one other cognitive function such as language or executive functions, thus impacting upon behavior and interfering with social or occupational functioning (American Psychiatric Association, 2000). Diagnosis: Until Recently, most of our understanding of the physiological pathology surrounding the terrifying decline of the patients mental faculties, their loss of memory, loss of language, loss of social connections of a whole lifetime, came from information gleaned from post mortem autopsies, way too late to do anything for hapless patients who eventually succumb to the disease after years and years of decline. The clear presenting common factor in all cases has been two identifiable abnormalities of structure, the first being the accumulation of plaques called Beta Amyloid Plaques. These plaques are caused by the bundling of protein fragments called amyloid precursor protein which collect in the spaces between neurons in the brain. The second abnormal factor occurs within the

Neurons themselves, a series neurofibrillary tangles of abnormal, insoluble clumps of a protein called tau. Normally these neurofibrils form part of the transport system within the neuron itself, for if you picture a neuron, it is incredibly long in comparison to the cell body size, with dendritic branches receiving neural impulses from the thousands of connected neurons, as well as the axon, which is the afferent branch carrying each neurons impulses to its connected neurons. The neurofibrils, together with the microtubules, can be visualized as a railway track with the track itself and the sleepers securing the track in position. It seems that the sleepers come loose and the line falls apart, and the train transporting nutrients and materials to the far reaches of the neuron becomes derailed. The two above mentioned anomalies lead to the functional decline of the neuron, as the cell thrives on synaptic connections with other cells, and this function is seen as the Raison Detre of neurons, and form the billions of trillions of possible connection combinations which allow our brains, in the words of Dr VS Ramachandran, to contemplate the universe, to contemplate the concept of infinity, and to contemplate itself contemplating infinity!! The net effect results in a generalized atrophy of the brain which manifests in the ongoing deterioration of short term memory, loss of speech and other executive functions and deepening dementia as the disease progresses. More recently, however, brain imaging techniques have been developed, which for the first time allow doctors to see and measure the presence and development of Beta Amyloid Plaques and Neurofibrillary tangles in live patients. This has opened the possibility of studying the correlation between the plaques and tangles to the progress of the disease in real time, and studies conducted at the University of Kentucky that

there is a correlation. In addition, they have discovered that many people develop the amyloid plaques and the neurofibrillary tangles at an early age, but are asymptomatic, until it reaches a point where the levels of plaque begin to present with signs of degeneration. This means is that we now have access to technology which gives us early warning, a bit like RADAR allowed us to see approaching bombers hours before we could actually see them, giving a window of opportunity to do something about the condition while still asymptomatic. This has been referred to as risk markers or risk assessment, and recent studies at the said Kentucky University are being conducted into ways to forestall or avert the development of the disease. One of the exciting observations is that lifestyle plays an important part in the way that the disease progresses, and that even where the risk markers have become present, that lifestyle changes such as exercise and diet positively impact the progression of the disease. The Kentucky University is currently conducting trials to assess different types of exercise, different amounts of exercise and optimal regimens of exercise, with the view that exercise may be prescribed almost in the same way that drugs are deployed to treat other diseases. Additional risk factors which have been identified are levels of cortisol, linked to our levels of stress, which increases our risk of developing Alzheimers Disease (AD).

Tools for diagnosing probable Alzheimers disease include a medical history, a physical exam, and testspreferably over timethat measure memory, language skills, and other abilities related to brain functioning. Information provided by family members or other caregivers about changes in a persons day-to-day function and behavior also help in diagnosis. Currently, a definitive diagnosis of Alzheimers can be made only after a brain is autopsied after death. However, in specialized research facilities such as the NIAs network of 29 Alzheimers Disease Centers, clinicians may also use brain scans and biomarkers in blood and cerebrospinal fluid to help diagnose Alzheimers dementia in people who may or may not be participating in a clinical trial.

In other research it has been shown that Insulin resistance in peripheral tissue , a hallmark of type 2 diabetes, also develops in Alzheimers disease (AD) brains (Beeri MS, Middleton L). This means that by being physically active, maintaining good body mass index and a healthy diet, we can ameliorate our risk of developing AD. (Neurology 2012;78: 1290 1291.) Brain levels of insulin and insulin receptor (IR) are lower in AD, and insulin signaling impairments have been documented in both postmortem analysis and in animal models of AD (e la Monte SM. Insulin resistance and Alzheimers disease. BMB Rep. 2009;42(8):475481). Brain insulin signaling is particularly important for learning and memory (Chiu SL, Chen CM, Cline HT. Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo. Neuron. 2008; 58(5):708719.), suggesting that insulin resistance may contribute to cognitive deficits in AD. In research conducted by Theresa R. Bomfim,et al, promising results have been achieved with the use of anti diabetic drugs as a treatment for AD.

References:

An anti-diabetes agent protects the mouse brain from defective insulin Title: signaling caused by Alzheimer's disease- associated A oligomers. Bomfim, Theresa R.1 Forny-Germano, Leticia1,2 Sathler, Luciana B.1 Brito-Moreira, Jordano1 Houzel, Jean-Christophe2 Decker, Helena1,3 Silverman, Michael A.3 Kazi, Hala4 Authors: Melo, Helen M.1 McClean, Paula L.5 Holscher, Christian5 Arnold, Steven E.4 Talbot, Konrad4 Klein, William L.6 Munoz, Douglas P.7 Ferreira, Sergio T.1

De Felice, Fernanda G.1 felice@bioqmed.ufrj.br Journal of Clinical Investigation; Apr2012, Vol. 122 Issue 4, p1339-1353, Source: 15p, 6 Color Photographs, 1 Diagram, 2 Graphs Document Article Type:

Title:

National Institute on AgingAlzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease