HealthandDiets.com - Alzheimer's disease or senile dementia of Alzheimer's type is a neurodegenerativ

Alzheimer's disease or senile dementia of Alzheimer's type is a neurodegenerative disease which results in a loss of mental functions due to the deterioration of brain tissue. Its exact etiology (cause) is still unknown, but environmental as well as genetic factors are thought to contribute (mutations in at least four genes predisposing to Alzheimer's disease have been identified). Until the 1960s, the disease was thought to be uncommon, but later it was realized that much of what had been regarded as the normal process of aging was actually the result of this disease.

Clinical features of Alzheimer's disease

The typical visible symptom is progressive and chronic memory loss. Alzheimer's disease is also manifested in behavorial changes, which may include confusion, disorientation, sudden periods of defiance, abusive behavior, or violence, etc. in people who have no previous history of such behavior (rarely, an affected person experiences euphoria). Thus, Alzheimer's disease presents a considerable problem in patient management, as well. Average duration is approximately 10 years. The disease duration has been been noted to vary as very roughly half of the normal life expectancy of a healthy person of the same age as the patient in whom the Alzheimer's is diagnosed, subject to a maximum of 10 to 12 years for those diagnosed at a young age.

Pathology of Alzheimer's disease

There are several changes found in the brain in Alzheimer's disease. * The deposition of an abnormal protein outside nerve cells in the form of amyloid. These are called diffuse plaques and amyloid also forms the core of more organized plaques called senile or neuritic plaques. * The accumulation of abnormal filaments of protein inside nerve cells in the brain. The protein is called tau and is normally present to stabilise microtubules. In Alzheimer's disease, an abnormally phosphorylated form of tau protein accumulates as paired helical filaments. Tau accumulates:

o As masses of filaments inside nerve cell body termed neurofibrillary tangles o Inside nerve cell processes in the brain termed neuropil threads o Inside nerve cell processes that surround amyloid plaques - termed plaque neurites. * Amyloid accumulation in the walls of small blood vessels in the brain. Termed amyloid angiopathy (also called congophilic angiopathy) * Diffuse neuropathology, nerve cells and their processes including synapses die and are lost from key brain regions. This results in atrophy of the affected areas and enlargement of the ventricles. * Loss of synaptic contacts between neurons. May be related to the regulation of cell adhesion proteins by presenilins. The presenilins have been identified as part of the processing apparatus that produces the amyloid beta protein. There is also regional involvement of gross atrophy, and enlarged ventricles in the brain. Massive synaptic and dendritic loss is expected. The neurotransmitters serotonin, acetylcholine, norepinephrine, and somatostatin are at decreased levels. Glutamate levels are usually elevated. Many of these features can be seen with the microscope using special histological techniques and are only seen when the brain is examined after death.

Etiology of Alzheimer's Disease

Three competing hypotheses exist to explain the cause of the disease. The oldest hypothesis is the "cholinergic hypothesis". It states that Alzheimer's begins as a deficiency in the production of acetylcholine, a vital neurotransmitter. Much early therapeutic research was based on this hypothesis, including restoration of the "cholinergic nuclei". The possibility of cell-replacement therapy was investigated on the basis of this hypothesis. All of the first-generation anti-Alzheimer's medications are based on this hypothesis and work to preserve acetylcholine by interfering with acetylcholinesterases (enzymes that break down acetylcholine). Results had from these medicines have not been promising. In all cases, they have served to only treat symptoms of the disease and have neither halted nor reversed it. These results and other research have led to the conclusion that acetylcholine deficiencies may not be causal but are a result of widespread brain tissue damage, damage so widespread that cell-replacement therapies are likely to be impractical. The other two hypotheses are of generally equal acceptance. "Tau-ists" believe that the tau protein abnormalities come first and lead to a full disease cascade. "bA-ptists" believe that beta amyloid deposits are the causative factor in the disease. For example, the presence of the APP gene on chromosome 21 is believed to explain the high incidence of Alzheimer's disease in patients with Down syndrome (trisomy 21). The terms "tau-ist" and "ba-ptist" are used (lightheartedly) in scientific publications by Alzheimer's disease researchers. A third protein, alpha synuclein, which has already been shown to be important in Parkinson's disease, has recently been proposed as the etiological candidate, giving rise to the "syn-ners". By 2004, several researchers have come to the conclusion that Alzheimer's disease may be a "triple-protein pathology", wherein interactions among all three lesions are what give rise to Alzheimer's disease, rather than any one of the three. There is compelling evidence that genetic predispositions underlie the development of Alzheimer's disease. However, the most obviously genetic cases are also the rarest. Most cases identified are 'sporadic' with no clear family history. It is probable that environmental factors have to interact with a genetic susceptibility to cause development of disease. Head injury has been consistently shown to be linked to later development of Alzheimer's disease in epidemiological studies. In addition, small cranial diameter has been shown to correlate well with early onset of recognizable symptoms. The most commonly accepted explanation for this last feature is that larger brains simply may have more cells that can afford to be lost. Inheritance of a specific variation of the ApoE gene (epsilon 4) is regarded as a risk factor for development of disease, but large-scale genetic association studies raise the possibility that even this does not indicate susceptibility so much as how early one is likely to develop Alzheimer's. Intriguing work is currently going on investigating the possibility that the regulatory regions of various Alzheimer's associated genes could be important in sporadic Alzheimer's, especially inflammatory activation of these genes. Studies have not shown strong link with toxins, vitamins, metals or diet, although rabbits fed a high-cholesterol diet in the presence of copper ions in their water did develop amyloid brain lesions and cognitive deficiencies. Therefore, it is hasty and premature to dismiss any and all environmental effects out of hand. There have been studies that link aluminium to the progression of Alzheimer's, but the results from these studies have not been confirmed and are not widely accepted by Alzheimer's experts. Rare cases are caused by dominant genes that run in families. These cases often have an early age of onsent. Mutations in presenilin-1 or presenilin-2 genes have been documented in some families. Mutations of presenilin 1 (PS1) lead to the most aggressive form of familial Alzheimer's disease (FAD). Evidence from rodent studies suggests that the FAD mutation of PS1 results in impared hippocampal-dependent learning which is correlated with reduced adult neurogenesis in the dentate gyrus. Mutations in the APP gene on chromosome 21 can also cause disease.

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Clinical features of Alzheimer's disease

Pathology of Alzheimer's disease

Etiology of Alzheimer's Disease