Researchers have shown that they can detect tiny, misfolded protein fragments in cerebrospinal fluid taken from patients. Such fragments may be an early indicator of Alzheimer's disease. The findings reported in the journal Cell Reports lend hope that doctors might soon have a way to diagnose the disease before extensive brain damage and dementia have set in. The new research suggests that precursors of amyloid plaques, so-called Aβ oligomers, may be circulating in the body years before cognitive symptoms arise.
In the new study, researchers used a technology they developed earlier for the detection of the misfolded proteins responsible for prion diseases. Their protein misfolding cyclic amplification (PMCA) technology works by amplifying existing misfolded proteins and then breaking them up into smaller pieces. When mixed with the equivalent, normal protein, the fragments act as seeds for the formation, in the case of Aβ, of amyloid clumps like those found in the Alzheimer's brain.
The researchers showed that PMCA technology can detect Aβ oligomers at very low concentrations. In principle, it might be possible to detect even a single particle of misfolded Aβ. Most importantly, lead author Claudio Soto, PhD, and colleagues were able to distinguish between patients with Alzheimer's disease and those with other neurodegenerative or neurological disorders with 90% sensitivity and 92% specificity by applying their test to cerebrospinal fluid samples. The next step, Soto says, is to adapt the technology for use with blood or urine samples, which would be much easier to obtain for screening healthy people for biochemical signs of Alzheimer's disease. Read the study abstract.