Results from a clinical validation study show that Diadem’s AlzoSure, a blood-based biomarker test, accurately predicts progression to Alzheimer’s disease (AD) up to six years prior to diagnosis. The data from the retrospective longitudinal study has been made available in a medRxiv preprint before its submission to the Journal of Neuroscience.
The AlzoSure Predict prognostic biomarker Alzheimer’s blood test detects levels of an unfolded conformational variant of the p53 protein in the blood using a proprietary antibody called U-p53AZ.
Non-invasive plasma tests are an ideal way to monitor AD onset and progression before the occurrence of cognitive decline and pathogenic accumulation of amyloid beta plaques in the brain. However, biomarker tests are challenging to develop due to the identification of appropriate disease-specific biomarkers, and designing test assays that can detect them with high accuracy and sensitivity.
The new study shows that the prognostic performance of AlzoSure Predict was high with results consistent with previous studies. The test could predict AD dementia six years before the appearance of symptoms in cognitively normal (CN) individuals or who had minor cognitive impairment (MCI) at baseline. The test achieved high accuracy with AUC values of 99 percent over the years of study follow-up. The AUC is a measure of discrimination; a high AUC denotes the probability of a biomarker being higher in a patient with the disease than in a control, healthy patient.
The results also provide confirmation on the test’s ability to discriminate between patients at different stages of cognitive decline, from asymptomatic to mild impairment to full AD dementia.
The longitudinal study involved 482 patients from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who were followed for up to 12 years. Results from the study show that Diadem’s Alzheimer’s blood test demonstrated superiority to standard PET imaging and other AD diagnostics, as well as AD-related genetic biomarkers.
p53 in Alzheimer’s
The p53 protein is a transcription factor and tumor suppressor involved in regulation of key cellular processes including the cell cycle and programmed cell death (apoptosis). It is known as the “guardian of the genome” given its central role in the DNA damage response. It senses damage to DNA and triggers protective mechanisms to try to repair it; if damage is extensive and beyond repair, it triggers death of the cell. Mutations that lead to loss of p53 function, as well as loss of heterozygosity, underlie various cancers and pre-cancerous conditions such as Li-Fraumeni syndrome, which is a rare hereditary disorder that increases the risk of developing many types of cancer.
In AD, altered levels and activity of p53 are implicated in disease pathology. The protein maintains hyperphosphorylation of neuronal tau proteins, and amyloid beta peptides contribute to maintaining pools of the conformational, misfolded variant of p53.
Diadem’s Alzheimer’s Blood Test
The Diadem AlzoSure Predict assay uses a proprietary antibody, U-p53AZ, to measure blood levels of the unfolded conformational p53 variant.
“These study results reflect years of innovative research by Diadem scientific co-founder Professor Daniela Uberti, a leader in investigating the role of this conformational p53 variant in the development of Alzheimer’s disease,” said Paul Kinnon, CEO of Diadem, in a company press release.
“The new data reinforce and validate our prior studies showing that AlzoSure Predict can identify individuals who will progress to Alzheimer’s dementia years before symptoms are evident, and it does so more accurately than established diagnostic tools such as PET imaging of amyloid b load. Best of all, our biomarker test is blood-based, simple, and affordable, making it accessible for a variety of applications, including broad-based patient screening.”
Kinnon added that Diadem is aiming to complete additional validation studies over the next several months with a global launch in the works for next year.
Diadem says AlzoSure Predict is being developed as “a simple, non-invasive plasma-based biomarker test to accurately predict the probability that a patient with asymptomatic mild cognitive impairment will progress to Alzheimer’s dementia.”
The company is currently conducting a follow-up study of its Alzheimer’s blood test using additional longitudinal data from different cohorts and centers in Europe and the US to validate the new findings. The study will compare and correlate the potential of U-p53AZ as a blood-based biomarker with other conventional AD markers under study. Results from this study are expected later this year.