Alzheimer's Disease

This is a working-paper/pre-print of the first chapter of my PhD thesis:

Alois Alzheimer in 1907 reported a study of one of his patients with “an unusual illness of the cerebral cortex” (Alzheimer 1907, Stelzmann 1995). Alzheimer details the symptoms of his patient suggesting that they were so unusual that the patient could not be classified as having one of the recognized illnesses.

The first symptom the 51-year-old woman showed was the idea that she was jealous of her husband. Soon she developed a rapid loss of memory. She was disoriented in her home, carried things from one place to another and hid them, sometimes she thought somebody was trying to kill her and started to cry loudly. ... As the illness progressed, these phenomena which are to be interpreted as complex symptoms appear sometimes stronger, sometimes weaker. But they are never severe. On the other hand, the imbecility of the patient increased in general. Her death occurred after four and a half years of illness. At the end, the patient was lying in bed in a fetal position completely pathetic, incontinent. In spite of all nursing care, she had developed bedsores. ... The post-mortem showed an evenly atrophic brain without macroscopic focal degeneration. ... the nucleus and the cell itself disintegrate and only a tangle of fibrils indicates the place where a neuron was previously located. ... Many neurons, especially the ones in the upper layer, have completely disappeared. ... Distributed all over the cortex, but especially numerous in the upper layers, there are minute miliary foci which are caused by the deposition of a special substance in the cortex. ... Considering everything, it seems we are dealing here with a special illness.

More than a century now, indeed Alzheimer was right that he was dealing with a special illness which is now named after himself, as Alzheimer’s Disease (AD). Ever since this first reporting, several studies have been performed in the past century and in particular the last couple of decades. However, the exact mechanisms of AD and its causes are poorly understood, and there is no cure till date.

Progressive decline of cognitive functions of the human brain associated with gradual death of neurons is a more general condition named dementia. Prominent symptoms of dementia are loss of memory, mood changes, and problems with communication and reasoning. AD is the most common form of dementia contributing to \(60-70\%\) of cases (WHO 2015). It primarily affects the aging population and the risk increases with age. The increment of longevity in most parts of the world due to the advancement of medical science and consequently better health care can cause a significant rise in the incidence of AD in coming years. Thus, it is imperative to improve our understanding of AD to alleviate the growing socio-economic impact of AD in the world.

\label{fig:normalVsAD_Bird2008} Figure reproduced from (Bird 2008) comparing normal adult brain (top) with Alzheimer brain (bottom) which shows widespread diffuse cortical atrophy and ventricular enlargement in the brain with AD.