Current status: Alzheimer's Disease.

lzheimer's disease (AD) is a specific type of neurodegenerative dementia characterized clinically by a progressive loss of memory and other aspects of cognition and pathologically by the presence of neurofibrillary tangles, amyloid plaques, and neuronal cell death1. Alois Alzheimer was the first physician to describe the neurohistopathological aspects of AD in 1907 in a 55-year-old woman. It accounts for 50-60% of the causes of senile dementia. However, it has become clear that AD can occur in any decade of adulthood and is the most common cause of dementia in the elderly. 20-15% of the population over age 65 and almost 50% of the population over 85 has some degree of dementia2. There are considerable medical, financial, social and emotional costs associated with the burden of caring for patients with AD. Pathophysiology of AD The exact pathophysiology of AD is still unsettled. The different risk factors for development of AD are: old age, female gender, family history of dementia, ApoE ε4 allele (in non familial AD), lower educational attainment, head trauma with loss of consciousness, thyroid dysfunction, no post-menopausal-estrogen therapy, different environmental factors like aluminium, mercury, viruses, prions etc, inflammation of the brain and Down's syndrome 3,4,5. Early changes in AD include atrophy of the hippocampus and entorhinal cortex. There is loss of cholinergic and other neurons in the cerebral cortex and nucleus basalis of Meynert and related nuclei that contain the cell bodies of cholinergic neurons which project to hippocampus, amygdala and all of the neocortex 2. Reduction in nicotinic cholinergic receptors is reports in AD. It is likely that 4 containing nicotinic receptor subtypes are reduced predominantly in Ad 6. The cause of the neuronal degeneration in AD is still not confirmed. The cytopathologic hallmarks of the disease are intracellular NEUROFIBRILLARY TANGLES and extracellular NEURITIC SENILE PLAQUES. Neurofibrillary tangles are made up in part of hyperphosphorylated forms of the tau protein that normally binds to microtubules. The neuritic plaques contain a central core that includes β – amyloid (Aβ), ApoE, proteoglycans and other proteins. Aβ is a 4.2-k Da protein of 39 – 42 amino acids that is derived proteolytically from amyloid precursor protein (APP) by the enzymes α, β and γ secretases. Two types of Aβ are found – Aβ-40 and Aβ42 forms insoluble aggregates 4,7. There are two proteins found in the membranes of cellular organelles: Presenilin-1 (coded by a gene on chromosome 14) and Presenilin-2 (coded …