In the context of Alzheimer's disease, the data for anti-amyloid immunotherapies, the most recent of which do effectively clear the aggregation of amyloid-β in the brain, is not compelling. Clinical trials and following studies show minimal to no benefit to patients even at earlier stages of the condition. There is some hope in the research and development community, where the amyloid cascade hypothesis remains dominant, that moving to even earlier deployment of these therapies might prevent the emergence of the condition, but the data obtained to date does not inspire optimism on this front. Other directions are much needed, perhaps restoration of cerebrospinal fluid drainage, for example, or more of a focus on chronic inflammation in brain tissue.
Alzheimer's disease is a neurodegenerative disorder and the most common cause of dementia. Aggregated amyloid-beta protein deposits are implicated in its pathogenesis. Amyloid-beta-targeting monoclonal antibodies (sometimes represented as Aβ-mAbs) are potentially disease-modifying for Alzheimer's disease: through the clearance of amyloid in the brain, they may slow cognitive and functional decline. In this meta-analysis we assess the clinical benefits and harms of amyloid-beta-targeting monoclonal antibodies aducanumab, bapineuzumab, crenezumab, donanemab, gantenerumab, lecanemab, ponezumab, remternetug, and solanezumab in people with mild cognitive impairment or mild dementia due to Alzheimer's disease.
The effect of amyloid-beta-targeting monoclonal antibodies on cognitive function and dementia severity at 18 months in people with mild cognitive impairment or mild dementia due to Alzheimer's disease is trivial, while on functional ability, it is small at best. Amyloid-beta-targeting monoclonal antibodies increase the risk of amyloid-related imaging abnormalities. Both desirable outcomes and adverse events were inconsistently reported in the studies included in the review. Successful removal of amyloid from the brain does not seem to be associated with clinically meaningful effects in people with mild cognitive impairment or mild dementia due to Alzheimer's disease. Future research on disease-modifying treatments for Alzheimer's disease should focus on other mechanisms of action.
Link: https://doi.org/10.1002/14651858.CD016297
View the full article at FightAging
