**A new study claims that it observed that higher levels of soluble amyloid-β42, one of the main forms of amyloid-β associated with Alzheimer's disease, is associated with better cognition. Yet there is no description of a mechanism of action, this is just a correlation study.
Source: Nephron via Wikipedia
It is known that reduced CSF Aβ42 levels in Parkinson's disease and dementia with Lewy bodies predict cognitive impairment and a more aggressive disease course and correlate with postmortem β-amyloid plaques in the brain. Recently it was shown the same phenomenon also appears in Alzheimer's disease.
This article brings new insight in that it suggests that increasing the levels of CSF's Aβ42 with anti-Aβ monoclonal antibodies benefits Alzheimer's disease.
The authors analyzed data from 25,966 AD patients in 24 clinical trials of anti-Aβ drugs that either lowered or increased CSF Aβ42 levels. They focused on long-term (12 months or more) placebo-controlled trials of anti-Aβ drugs published up to November 2023. The scientists examined the effects of new anti-amyloid-β (Aβ) monoclonal antibodies on Alzheimer’s disease (AD). These antibodies are designed to reduce amyloid plaques in the brain, which are associated with AD. While their primary effect is to reduce amyloid in the brain, some also increase levels of the 42-amino acid isoform (Aβ42) in cerebrospinal fluid (CSF).
The study evaluated changes in cognitive function and clinical status and compared these changes with alterations in CSF Aβ42 and brain amyloid measured by PET imaging. Increased levels of CSF Aβ42 were associated with slower cognitive and clinical decline, as measured by ADAS-Cog and CDR-SB.
The authors hypothesized that normal, soluble Aβ42 in the brain is crucial for neuron health and that the loss of Aβ42, rather than the buildup of plaques, drives Alzheimer's, but it's not apparent in the article if this is verified.
Yet, as stated above there is no mechanism of action described, in my opinion, scientists focus too much on drugs using brute force. They seem to think only in terms of removing or more rarely increasing the level of some molecules, based on correlations, but not on complex descriptions involving multiple biological systems.