Alzheimer’s disease (AD) is one of the most challenging and costly disorders with an incidence of 5.8 million people in the United States in 2019 by rising expectantly up to 13.8 million affected people in the 2050s . While Amyloid-β is a key neuropathological feature of AD , soluble Aβ in cerebrospinal fluid (CSF) is one of the most important biomarker for AD in clinical practice .
Since Biogen’s novel Amyloid-β targeting therapy, its monoclonal antibody Adacanumab, reduces amyloid plaques in the brain and most likely improve cognition , latest causal therapies might be close to clinical implementation . However, due to the cost intensive therapy and potential side effects, patients need to be selected carefully to exclusively include patients with an underlying Alzheimer’s pathology before receiving this kind of therapy. In particular, the recently introduced limbic-predominant age-related TDP-43 encephalopathy (LATE) is a clinically serious differential diagnosis, contributing to about 15–20% of the false-positive AD cases in elderly patients . These patients will most likely not benefit from novel Aβ based therapies such as Adacanumab. Therefore, there is a high need for screening assays to select patients with possible AD neuropathological changes.
Many studies have shown the pre-analytical characteristics of CSF biomarkers. For example, Lewczuk et al. showed that CSF Aβ is stable up to seven days at room temperature (RT) . However, the composition of blood defers from CSF. Several studies have suggested plasma Aβ, in particular the Aβ42 to Aβ40 peptide ratio (Aβ42/40) as a potential biomarker for AD [8–10]. There is currently very limited data on pre-analytic handling conditions of blood samples to measure peripheral Aβ species. As recommended by the Blood-Based Biomarker Interest Group , Rózga et al. analyzed different handling conditions, however relevant storage conditions, in particular storage of whole blood at 4 °C are missing .
Due to the high demand of easy to access screening tools, we also studied handling and storage of capillary blood. Independent of any medical centers, capillary blood can be easily collected by oneself with a small finger insertion, comparable to blood sugar measurements, and sampled in microvettes®.
This study provides complementary data to the recently published study by Rózga et al , outlining potential sampling, handling and storage condition for a broad general practice to pre-screen patients for further AD diagnostics.