Alzheimer’s: Origins and Treatment
Professor Jürgen Götz, Director, Clem Jones Centre for Ageing Dementia Research (CJCADR) at the Queensland Brain Institute explains the current status of research into the prevention and cure of dementia.
Dementia is a general term for the decline in mental ability that is severe enough to interfere with our daily life. Common signs of dementia include memory loss, decreased or poor judgement, confusion in relation to time or place, loss of communication skills, difficulties in planning or solving problems and inappropriate behaviour.
Alzheimer’s disease is the most common form of dementia, accounting for approximately 70% of all cases. Unfortunately, dementia is on the rise, reaching dramatic proportions. A major reason is that age is the most important risk factor for the disease, a down-side of the increased life expectancy of many societies, including that of Australia. In fact, Australia is placed among the top 10 OECD countries as far as life expectancy is concerned.
By 2030, there will be over 560,000 people with dementia in Australia alone and almost 1 million by 2050. Worldwide figures suggest that 36 million people are currently living with dementia, and it has been predicted that within two decades, dementia will become the third greatest source of health and residential aged care spending.
Prof. Jürgen Götz, Director, Clem Jones Centre for Ageing Dementia Research (CJCADR) at the Queensland Brain Institute – right. Research Assistant Matt Pelekanos is on the left.
Our knowledge of Alzheimer’s disease dates back to 1907 when the Bavarian-born psychiatrist and neuropathologist Alois Alzheimer described his first case, a patient named Auguste Deter, who died soon after of presenile dementia. Post-mortem examination of her brain revealed two pathological changes which were named plaques and tangles. Their visualization was made possible with the development of new histological staining methods that had recently been developed. Emil Kraepelin, the then Director of the Royal Psychiatric Clinic in Munich, Germany, where Alzheimer was employed, published a textbook in 1910 and named presenile (i.e. early-onset) dementia after Alzheimer.
Around the same time, the Czech psychiatrist and neuropathologist Oskar Fisher described plaques and tangles in senile (i.e. late-onset) forms of dementia. Today we know that both presenile and senile dementia are clinically and histopathologically very similar, except that the former starts much earlier.
Presenile dementia is caused by gene mutations and today we know that Auguste Deter carried a mutation in the presenilin gene. After Alois Alzheimer’s and Oskar Fischer’s discoveries, there was a standstill for many decades until, in the second wave of discoveries, in the 1980s, new biochemical methods were developed that helped to identify the peptide amyloid- β (or Aβ) as the major constituent of the plaques and the protein tau as the major constituent of the tangles.
Alzheimer’s disease is the most common form of dementia, accounting for approximately 70% of all cases.
Close to a decade later, a third wave of discoveries was aided by new sequencing and genetic methods, allowing the identification of gene mutations (including in the aforementioned presenilin) in familial cases of Alzheimer’s disease and related dementias such as frontotemporal dementia, which helped to pave the way for so-called transgenic animal models, that carry these gene mutations, develop a mild form of Alzheimer’s disease (or frontotemporal dementia) and have since been instrumental in the development of new therapeutic strategies.
At present, there is no cure for Alzheimer’s disease or any form of dementia. Current treatments, including acetylcholinesterase inhibitors and memantine, are mainly symptomatic, but strategies that directly target the underlying pathology are currently in development.
These approaches, which aim either to prevent the accumulation of Aβ and tau, or to assist in their clearance, include blockade of Aβ generation with β-secretase inhibitors, and targeting of Aβ, and more recently tau, with active and passive immunization. However, should passive immunization prove effective, the cost will be a critical issue; extrapolating its use in cancer, the estimated cost exceeds US$25,000 per patient per year.
Not only will this cost challenge the healthcare systems of many countries, but it will also raise ethical issues about how to make these vaccines widely available. As the Director of the Clem Jones Centre for Ageing Dementia Research (CJCADR) at the Queensland Brain Research, I oversee several research groups whose goal is to understand the pathogenesis of Alzheimer’s disease, using cellular and animal models, in order to develop novel therapeutic approaches.
This includes the development of novel vaccines for the tau pathology of the disease and a novel scanning ultrasound-based approach that greatly assists in the clearance of Aβ from the brain of Alzheimer’s mouse models and the restoration of memory functions. It is hoped that one of these approaches will advance into clinical trials, not necessarily to completely halt the disease, but to delay it to such an extent that it does not manifest clinically within the lifetime of at-risk people.
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