A simple blood test, combined with brief memory tests, has shown who will develop Alzheimer’s disease in the future with a high degree of accuracy.
Combining phosphorylated tau plasma (p-tau), APOE genotype, and 10-minute memory and executive function test scores predicted onset of Alzheimer’s disease within 2 to 6 years in people with memory impairment with 90% certainty, Oskar reported Hansson, MD, PhD, and Sebastian Palmqvist, MD, PhD, both at Lund University in Sweden and colleagues.
When dementia experts looked at the same patients, they were about 71% accurate, the researchers noted in Nature medicine.
“We show for the first time that a rapid and cost-effective diagnostic algorithm clearly outperforms the clinical workup typically performed today when it comes to predicting Alzheimer’s dementia,” said Hansson. MedPage today.
To build their prediction algorithms, the researchers studied 340 people with mild cognitive symptoms in Sweden. BioFINDER cohort. Participants were between 60 and 80 years of age, had a baseline Mini Mental Status Examination (MMSE) score of 24 to 30, and did not meet criteria for any dementia. The primary outcome measure was prediction of progression to Alzheimer’s dementia compared to any other dementia, or of not progressing, in 4 years.
The researchers assessed the demographics, APOE4 genotype, cortical thickness, cognitive measures, and plasma and cerebrospinal fluid (CSF) markers, first looking for the best fit, then omitting variables to find simpler algorithms with similar predictive power. They used data from 543 participants in the Alzheimer’s Disease Neuroimaging Initiative. (ADNI) as the validation cohort.
In 4 years, plasma p-tau217 alone predicted Alzheimer’s disease in the BioFINDER cohort with an area under the curve (AUC) of 0.83. Combining p-tau 217 plasma, memory tests, executive function tests and APOE precision increased to 91% (AUC 0.91, 95% CI 0.88-0.95, P
In DNAI, this model had a similar AUC (0.90) using p-tau181 plasma instead of p-tau217. In 2 and 6 years, similar models had AUCs of 0.90 to 0.91 in both cohorts. The use of CSF p-tau, amyloid beta, and neurofilament lumen instead of plasma biomarkers did not significantly improve accuracy.
Tau blood phosphorylated biomarkers have great potential in Alzheimer’s disease, said Nicholas Ashton, PhD, of Gothenburg University in Sweden, who was not involved in the study. “They offer an inexpensive and less invasive alternative to understanding what is going on at the molecular level in the brain,” he said. MedPage today.
Blood tests will be useful both for clinicians and for recruiting people into therapeutic trials for drugs specifically targeted for Alzheimer’s disease, Ashton noted.
Both p-tau217 and p-tau181 performed well in this analysis, he added. “There has been some debate about which is superior, but this study shows that – in combination with cognitive testing and genetic testing – it doesn’t matter what type of phospho-tau biomarker you use: they both gave the same. power of prediction. “
The algorithm is under development for clinics without access to advanced diagnostic instruments, Palmqvist said in a statement. “In the future, therefore, the algorithm could make a major difference in the diagnosis of Alzheimer’s disease in primary health care,” he noted.
So far, it has only been tested on patients who have been examined in memory clinics, he added. “We hope that it will also be validated for use in primary health care as well as in developing countries with limited resources.”
Last update May 30, 2021
The study was funded with support from the Swedish Research Council, Swedish Alzheimer Foundation, Swedish Brain Foundation, Knut and Alice Wallenberg Foundation, Marianne and Marcus Wallenberg Foundation, Skane University Hospital and ALF funding, as well as Lund University’s MultiPark Multidisciplinary Research.
Researchers reported relationships with Hoffman-La Roche, Geras Solutions, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, CogRx, Fujirebio, AlzeCure, Abcam, Axon, Biogen, JOMDD / Shimadzu, Julius Clinical, Eli Lilly, MagQu, Novartis, Eisai, GE Healthcare, Pfizer, AC Immune and Brain.