Systematic review of PPAV11 proteomic signature shows high accuracy for Alzheimer's disease diagnosis and prognosis

This systematic review assesses the performance of PPAV11, a molecular signature comprising eleven consistently dysregulated proteins, for Alzheimer's disease. The authors analyzed cerebrospinal fluid samples from discovery studies and independent validation cohorts, totaling n=759 and n=1,198 samples respectively. The signature was compared against thirteen published signatures to evaluate diagnostic accuracy and prognostic capacity.

The review reports high diagnostic accuracy for the PPAV11 signature, with an area under the curve exceeding 0.94. For prognostic capacity, the analysis found a significant ability to predict conversion from cognitive unimpaired to amnestic mild cognitive impairment or Alzheimer's disease and mild cognitive impairment, with a hazard ratio greater than 4.96 and a p-value of 0.004. Additionally, the signature demonstrated significant prognostic capacity for predicting progression from amnestic mild cognitive impairment to Alzheimer's disease and dementia, with a hazard ratio greater than 3.23 and a p-value of 3.13x10-7.

The authors note that establishing reproducibility is an important criterion for proteomic biomarker prioritization. They aim to define a stable molecular signature for integrated Alzheimer's disease diagnosis and prognosis. The review does not report adverse events or tolerability data. The findings are intended to support the selection of stable biomarkers rather than to establish clinical causality.