Alzheimer’s & Dementia | March 23, 2024

Islam T, Kvartsberg H, Sehrawat A, Kac PR, Becker B, Olsson M, Abrahamson EE, Zetterberg H, Ikonomovic MD, Blennow K, Karikari TK.

Alzheimers Dement. 2024

https://doi.org/10.1002/alz.13711

This study was performed using Simoa Homebrew assay(s).

Abstract

INTRODUCTION

Tau aggregation into paired helical filaments and neurofibrillary tangles is characteristic of Alzheimer’s disease (AD) and related disorders. However, biochemical assays for the quantification of soluble, earlier-stage tau aggregates are lacking. We describe an immunoassay that is selective for tau oligomers and related soluble aggregates over monomers.

METHODS

A homogeneous (single-antibody) immunoassay was developed using a novel anti-tau monoclonal antibody and validated with recombinant and brain tissue–derived tau.

RESULTS

The assay signals were concentration dependent for recombinant tau aggregates in solution but not monomers, and recognized peptides within, but not outside, the aggregation-prone microtubule binding region. The signals in inferior and middle frontal cortical tissue homogenates increased with neuropathologically determined Braak staging, and were higher in insoluble than soluble homogenized brain fractions. Autopsy-verified AD gave stronger signals than other neurodegenerative diseases.

DISCUSSION

The quantitative oligomer/soluble aggregate-specific assay can identify soluble tau aggregates, including oligomers, from monomers in human and in vitro biospecimens.