Targeted proteomic biomarker profiling using NULISA in a cohort enriched with risk for Alzheimer's disease and related dementias

Abstract

The NULISAseq pTau217 assay was comparable to the Simoa pTau217 assay, both utilizing the ALZpath antibody, in detecting amyloid positron emission tomography (PET) positivity, each with areas under the curve greater than 90%. Nineteen proteins were differentially expressed in participants with mild cognitive impairment (MCI) compared to those who were unimpaired. Markers of non-AD proteinopathies such as pTDP43-409, oligomeric alpha-synuclein, and huntingtin (HTT), were among those upregulated in MCI. High levels of plasma pTDP43-409 were associated with worsening hippocampal atrophy and cognitive decline, clinical indicators of limbic-predominant age-related TDP-43 encephalopathy (LATE), compared to those with low pTDP43-409.