Biomarkers for Alzheimer’s disease – spinal taps, brain scans, blood tests and the critical role of brain donation

By Professor Simon Lovestone

Professor of Old Age Psychiatry, NIHR Biomedical Research Centre for Mental Health, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF

Suppose you have memory problems and go to your doctor - what happens next? At best, and the best is not always achieved, then an assessment of memory and other cognitive function is made and, in some cases, a referral is made to a memory clinic where there may be more memory tests and perhaps a brain scan. If the outcomes of these tests are not severe enough to warrant a clear-cut diagnosis then, usually, the cognitive tests are repeated after a year to see if they have got worse. This is unsatisfactory as the wait must seem interminable to patients and their relatives. For professionals too, not being able to make an early diagnosis is frustrating.

When treatments for Alzheimer's disease (AD) go beyond symptomatic treatment to therapies for the illness itself, this wait will be unacceptable since it is in this early phase, before dementia is established, that the drugs are most likely to be effective. This, then, is one of the most important drivers for research into 'biomarkers' of AD. A biomarker is a biological signal that can be detected for diagnosis, ideally very early and before doctors are currently able to diagnose the condition. Biomarkers are also useful as the basis of tests for measuring how a disease is progressing. This latter use of biomarkers would be especially useful in research to find new treatments for dementia. Currently clinical trials rely almost entirely on memory tests which are sometimes less reliable than we would like as measures of disease. A biomarker that reflected the disease progression in the brain would be immensely useful as a measure against which to judge new treatments.

Brain Amyloid Imaging — FDA Approval of Florbetapir F18 Injection

Florbetapir F18 Scan Usage: Information Summary

A negative florbetapir scan:
• indicates sparse to no neuritic plaques.
• is inconsistent with a neuropathological diagnosis of Alzheimer's disease at the time of image acquisition.
• reduces the likelihood that a patient's cognitive impairment is due to Alzheimer's disease.
A positive florbetapir scan:
• indicates moderate to frequent amyloid neuritic plaques.
• may be observed in older people with normal cognition and in patients with various neurologic conditions, including Alzheimer's disease.
Important florbetapir scan limitations:
• A positive scan does not establish a diagnosis of Alzheimer's disease or other cognitive disorder.
• The scan has not been shown to be useful in predicting the development of dementia or any other neurologic condition, nor has usefulness been shown for monitoring responses to therapies.