Authors:

Oliver Zhang

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About Paper:

Alzheimer's disease (AD), the most common form of dementia worldwide, is characterized by the abnormal accumulation of soluble oligomers of B-amyloid peptide (ABO) and neurofibrillary tangles formed by hyperphosphorylated Tau. There is significant evidence supporting that AD pathogenesis begins years before symptoms appear, with neurotoxic ABOs playing a central role in disease triggering by contributing to synaptic dysfunction and neuronal death. Even though ABOs are hypothesized as a key biomarker for early AD diagnosis, diagnostic challenges remain, as non-invasive methods for early and definitive confirmation are scarce, along with antibodies that specifically target and discriminate among soluble toxic species. Amongst the antibodies selected against ABOs, the single chain fragment variable (scFv) NUsc1 demonstrates reliable selectivity to AD-relevant neurotoxic ABOs and serves as a prime candidate for their detection. We conducted a supersensitive ELISA with phage-bound NUsc1, where we used the phage-displayed version of the scFv fragment to detect ABO concentrations in AD mice brain homogenates, human brain homogenates, and lastly human CSF samples. The assay successfully detected ABOs in brain homogenates from both mice and humans. More importantly, it also detected ABOs in human cerebrospinal fluid (CSF), representing a significant advancement for clinical use. ELISA with phage-bound NUsc1 (pbNUsc'1) displayed significantly higher concentrations of ABOs in patients with AD compared to non-AD patients. These findings support the potential utility of this supersensitive assay as an early diagnostic tool for AD. By specifically targeting soluble, neurotoxic ABOs using the pbNUsc'1 antibody, this assay may provide a clinically relevant method for diagnosing and detecting AD. Further investigation will reveal potential correlation between CSF ABO levels and disease progression in patients without clinical AD.

Source:

Northwestern University

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Co-authors:

Oliver Zhang