title: Fibroblast aggregation rate converges with validated peripheral biomarkers for Alzheimer's disease.
abstract: The inaccuracy of the diagnosis for Alzheimer's disease (AD) has made its therapeutic intervention difficult, particularly early enough to prevent significant neurodegeneration and cognitive dysfunction. Here, we describe a novel, highly accurate peripheral diagnostic for AD patients based on quantitatively measured aggregation rate of human skin fibroblasts. The elevated aggregation rate with increasing cell density in AD cases is the basis of this new biomarker. The new biomarker was successfully cross-validated with two more mature assays, AD-Index, based on the imbalances of ERK1/2, and Morphology, based on network dynamics, and showed 92% overlap. A significant number of cases tested with this new biomarker were freshly obtained (n = 29), and 82% of the cases are hyper-validated cases, i.e., autopsy and/or genetically confirmed AD or non-Alzheimer's disease demented patients (Non-ADD) and non-demented age-matched controls. Furthermore, we show that by using a simple majority rule, i.e., two out of the three assays have the same outcome, we significantly increase the agreement with clinical AD diagnosis (100%). Based on the high accuracy of this strategy, the biomarker profile appears to accurately identify AD patients for therapeutic intervention.
authors.affiliation: Blanchette Rockefeller Neurosciences Institute, Morgantown, WV, USA.
authors.forename: Florin V
authors.initials: FV
authors.lastname: Chirila
authors.affiliation: Blanchette Rockefeller Neurosciences Institute, Morgantown, WV, USA.
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Khan
authors.affiliation: Blanchette Rockefeller Neurosciences Institute, Morgantown, WV, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Alkon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D015415:Biomarkers; D002449:Cell Aggregation; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Aggregation rate; Alzheimer's disease; cross-validation; majority rule; skin fibroblasts