Recently Published in Nature Communications and Alzheimer's & Dementia: Advances in the Diagnosis of Alzheimer's Disease Using Blood Biomarkers
Recent senior-author studies led by Thomas Karikari, PhD (Assistant Professor of Psychiatry), highlight advances in the diagnosis of Alzheimer's disease using blood biomarkers. Dr. Karikari’s research aims to further understand the molecular and biochemical basis of pathological brain changes that occur in Alzheimer’s patients, and to apply this knowledge to develop new biofluid-based diagnostic tools for clinical use. He was recently elected Alzheimer’s Disease Research Center Biomarker Core Steering Committee of the National Alzheimer's Coordinating Center.
Nature Communications
Dr. Karikari and his collaborators examined the diagnostic utility of plasma p-tau212 for the diagnosis of Alzheimer’s disease. In five cohorts, plasma p-tau212 showed high performances for Alzheimer’s disease diagnosis and for the detection of both amyloid and tau pathology, supporting plasma p-tau212 as a peripherally accessible biomarker of Alzheimer’s pathophysiology.
Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer’s disease neuropathology
Kac PR, González-Ortiz F, Emeršič A, Dulewicz M, Koutarapu S, Turton M, An Y, Smirnov D, Kulczyńska-Przybik A, Varma VR, Ashton NJ, Montoliu-Gaya L, Camporesi E, Winkel I, Paradowski B, Moghekar A, Troncoso JC, Lashley T, Brinkmalm G, Resnick SM, Mroczko B, Kvartsberg H, Kramberger MG, Hanrieder J, Čučnik S, Harrison P, Zetterberg H, Lewczuk P, Thambisetty M, Rot U, Galasko D, Blennow K, Karikari T.
Nature Communications 15, 2615 (2024). https://doi.org/10.1038/s41467-024-46876-7
Alzheimer’s & Dementia
The aggregation of tau to form fibrils and neurofibrillary tangles is a key feature of Alzheimer's disease. However, biochemical assays for the quantification of soluble, earlier-stage tau aggregates are lacking. Dr. Karikari and his collaborators, including Dr. Ikonomovic and Dr. Abrahamson in the Department of Neurology, developed and validated a new assay that preferentially binds to soluble tau aggregates. The assay signal increased corresponding to the total protein content, Braak staging, and insolubility of the sequentially homogenized brain tissue fractions.
Novel ultrasensitive immunoassay for the selective quantification of tau oligomers and related soluble aggregates
Islam T, Kvartsberg H, Sehrawat A, Kac PR, Becker B, Olsson M, Abrahamson EE, Zetterberg H, Ikonomovic MD, Blennow K, Karikari T.
Alzheimer's & Dementia. 2024; 20: 2894–2905. https://doi.org/10.1002/alz.13711
“These studies provide important insights into the discovery and analytical development of new surrogate markers that can be measured in simple blood samples for the detection of Alzheimer pathology and to monitor treatments. The new blood-based p-tau212 biomarker behaves equivalently to the more widely known p-tau217. In evaluation of a memory clinic cohort, we found that combining the two was more accurate at identifying individuals in the early stages of Alzheimer’s disease pathophysiology. The publication in Alzheimer’s and Dementia provides proof-of-concept toward the development of biochemical methods to detect aggregated forms of tau protein in human biofluids,” said Dr. Karikari, senior author of both studies.