Comment: New dementia classification highlights need for better diagnostics and personalised interventions

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Scientists and clinicians, led by Dr Pete Nelson (University of Kentucky), have described a new form of dementia that exhibits symptoms similar to Alzheimer’s disease, and suggest 20% misdiagnosis in patients over 80 years old.

Described in the journal BRAIN, Limbic-predominant age-related TDP-43 encephalopathy or ‘LATE’, has very similar symptoms to Alzheimer’s disease including memory problems, cognitive decline and mood disorders, but develops at a slower rate. The likeness between Alzheimer’s disease and LATE had caused confusion in the scientific community, as a large number of people who died in advanced age had symptoms of Alzheimer’s disease without the presence of amyloid and tau aggregates - the pathological hallmarks of the condition.

The discovery of LATE may provide an explanation for this discrepancy as it appears to be characterised by the aggregation of a different protein, TDP-43. Therefore, LATE may have a distinct disease mechanism from Alzheimer’s disease, and crucially require different therapeutic intervention.

 Professor Tara Spires-Jones, UK DRI at Edinburgh, said:

 “LATE pathology was found in over 1 in 5 people over 80 years of age, which implies that this disease is common in the oldest-old. The symptoms and genetic risk factors for late overlap with two other causes of dementia, Alzheimer’s disease and frontotemporal dementia. This paper is important because we know that dementia symptoms can be caused by many underlying diseases, and it is essential to understand what causes the diseases in order to develop targeted treatments.”

An important step forward in the dementia field, Professor Bart De Strooper, outlined the impact of the review:

“Dementia is a symptom of diseases with many different molecular causes. The current work is excellent as it makes us realise that the TDP-43 protein on its own is likely, along with the amyloid plaques and neuronal tangles in Alzheimer’s disease, a cause of late in life dementia.”

The work will help to define in better ways the different forms of dementia and makes it necessary to have a second look at the failed amyloid trials: maybe a part of the negative results are explained by the fact that we treated the wrong patients with the wrong drugs. Professor Bart De Strooper, UK DRI Director

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