Have we got the Leading Theory About Alzheimer’s all Wrong?
Monday, May 31st, 2021
The leading hypothesis on the cause of Alzheimer’s is looking shaky, following a new paper that pooled data from several studies to find that strategies to reduce amyloid levels in the brain do not improve cognition.[1]
The Amyloid Hypothesis
For several decades, a microscopic protein fragment called beta-amyloid found in the brains of people with the dementia, has been the primary suspect in the cause of the condition. Researchers argue that the build-up of this sticky compound disrupts the communication between brain cells, and ultimately kills them. The reasoning that has followed then, is that drugs that prevent or remove amyloid plaques should slow the onset of dementia. However, whilst amyloid may be a marker of dementia, it is not necessarily the cause. As any good crime show fan knows, identifying a suspect at the scene of the crime is not the same thing as proving responsibility.
Putting all the Data Together
Combining study results are more precise than results from individual trials. The American-based research team identified 14 randomised controlled trials of drugs for the prevention or treatment of dementia that targeted an amyloid mechanism. The studies typically included adults aged over 50 years with a diagnosis of mild cognitive impairment or Alzheimer’s Disease, and positive for amyloid in the brain at the study start. Each study provided data on both change in brain amyloid levels as measured by a PET scan and change in at least one cognitive test score.
Amyloid Reduction not Associated with any Cognitive Benefit
The combined results of the 14 trials found that a reduction in amyloid levels was not accompanied by a substantial improvement in cognition. This suggests that reducing amyloid levels is unlikely to have notable cognitive benefits within the timeframe of most typical clinical trials. It could be that amyloid reduction might have delayed effects on cognition that only manifest years later. If so, trials of anti-amyloid drugs would need to extend beyond the typical follow-up period, up to 2 years, to detect any benefit. However, a more feasible implication is that other potential targets – such as the protein tau – might merit more attention. This would fit would other evidence that amyloid plaques are also found in healthy individuals, and that not all people with dementia develop plaques.
