A blood test measuring amyloid beta aggregation seeding activity distinguished Alzheimer’s disease and mild cognitive impairment caused by Alzheimer’s disease from normal cognition and other dementias, according to a study published in the Chinese Medical Journal.
Researchers recruited 549 patients at Xuanwu Hospital, Capital Medical University, in China between December 2020 and May 2024. They assessed the test in a 120-patient discovery group before evaluating it in a separate validation group of 429 patients.
Both groups included cognitively unimpaired patients, patients with mild cognitive impairment (MCI) due to Alzheimer’s disease, patients with Alzheimer’s dementia, and patients with non-Alzheimer’s dementia. The non-Alzheimer’s group included patients with frontotemporal dementia, dementia with Lewy bodies, and Parkinson’s disease dementia.
The test used a technique called protein misfolding cyclic amplification to detect small amounts of misfolded amyloid beta in plasma. Repeated cycles of sonication amplified amyloid beta “seeds,” which can cause other amyloid beta proteins to misfold and aggregate. Researchers then measured this aggregation using a fluorescent dye.
Each sample was tested twice, and laboratory investigators did not have access to the patients’ clinical information. In laboratory experiments, the assay detected as little as one femtomole of synthetic amyloid beta oligomers. Results were available within 24 hours.
In the validation group, amyloid beta seeding activity was higher in patients with Alzheimer’s disease or MCI due to Alzheimer’s disease than in cognitively unimpaired patients and those with other forms of dementia.
The assay had an area under the receiver operating characteristic curve of 0.93 for distinguishing Alzheimer’s disease from normal cognition and 0.91 for distinguishing Alzheimer’s disease from non-Alzheimer’s dementia. The corresponding values for MCI due to Alzheimer’s disease were 0.92 and 0.90. Diagnostic performance was similar in the discovery and validation groups.
Cerebrospinal fluid biomarker results were available for 186 patients. In this subgroup, the plasma assay distinguished Alzheimer’s disease from non-Alzheimer’s dementia more accurately than the cerebrospinal fluid amyloid beta 42/40 and total tau/amyloid beta 42 ratios. Its performance was similar to that of the phosphorylated tau 181/amyloid beta 42 ratio.
Higher plasma seeding activity was also associated with poorer cognitive performance and greater dementia severity. Additional laboratory experiments supported that amyloid beta seeds were responsible for the measured activity.
The researchers noted several limitations. Diagnoses were based on clinical criteria rather than neuropathologic confirmation, and the study did not compare the assay directly with established plasma biomarkers such as phosphorylated tau 217. The cross-sectional design also meant the test’s ability to predict disease progression could not be assessed. Because all patients were Chinese, validation in other populations is needed.
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