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Feature Alzheimer’s Disease

Alzheimer’s disease: still a perplexing problem

BMJ 2014; 349 doi: (Published 08 July 2014) Cite this as: BMJ 2014;349:g4433
  1. Krishna Chinthapalli, associate editor, The BMJ and neurology specialty registrar, Royal Surrey County Hospital, UK
  1. kchinthapalli{at}

Funding for dementia research is being greatly increased in the UK. Krishna Chinthapalli examines the challenges after a century of frustratingly slow progress

“Dementia now stands alongside cancer as one of the greatest enemies of humanity,” said UK prime minister David Cameron at last month’s global dementia legacy event. He went on to announce the world’s biggest population study into dementias and a quadrupling of dementia research funding over the next decade. However, he was also aware of some of the huge challenges: “We don’t yet know anything like enough about how the brain becomes diseased . . . Only three out of 101 dementia drugs developed between 1998 and 2011 have made it to market.”1

Alzheimer’s disease, the commonest cause of dementia, was named over a century ago and exemplifies these challenges. Alois Alzheimer published his report “About A Peculiar Disease of the Cerebral Cortex” in 1907 after examining Auguste Deter, a 51 year old woman, in an asylum. He noted she was disorientated in time and place and that “her ability to retain information is impaired to the profoundest degree.”

What have we learnt about the pathogenesis of Alzheimer’s disease?

When Deter died, Alzheimer asked for her brain to be sent to his laboratory and found neurons containing “a tangled bundle of fibrils” and “storage of a peculiar matter into the cortex”—what we now know as neurofibrillary tangles and amyloid plaques, both considered pathological hallmarks of Alzheimer’s disease.2

Since that first study, understanding of how these lesions develop has been slow. Even by the 1980s, a review concluded that “the pathogenesis and aetiology of Alzheimer’s disease remain unknown territory.”3 Now, there are three main hypotheses.

The most popular model is the amyloid hypothesis. This is based on the pathological formation of the amyloid plaques seen by Alzheimer, which are directly toxic to cells as well …

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