Oligomeric Abeta levels in CSF, an appealing new biomarker
Through our partnership with Amorfix Life Sciences, we offer the assessment of oligomeric Abeta levels in brain and CSF, as an appealing read-out and biomarker in our proprietary APP-London and APPxPS1 transgenic models.
Already at the age of 2-3 months, i.e. long before the onset of amyloid deposition and plaque formation at 10-11 months, soluble oligomeric Abeta is present in brain and CSF of APP-London mice and their levels gradually increase with age (Figure 1, similar profiles are seen in our APPxPS1 model, albeit with different timing and severity). The coincidental timing with the pre-plaque onset of cognitive defects in this transgenic model is intriguing, given that increases of soluble Abeta also correlate with cognitive decline and neuropathological AD hallmarks in diseased brains.
Elevated oligomeric Abeta levels have also been observed in CSF of Alzheimer patients (e.g. as reported by Fukomoto et al., 2010 and presented by Amorfix Life Sciences at ICAD2011), where they have been proposed as a diagnostic marker for the disease as well as a surrogate marker for disease stage.
For getting more information on other interesting CSF biomarkers in reMYND’s APP and TAU transgenics, see the evolution with age of CSF Abeta42 in APP-London and CSF pan-tau in hTAU[P301L] in the parallel column discussing the potential of serial CSF draws in this context.
Figure 1. Aggregated Abeta in brain and CSF in APP-London mice prior to plaque formation. (A) Representative photo collection of anti-Abeta stained sections showing total plaque load in APP-London mice of different ages (proprietary anti-Abeta Nanobody®, reMYND/Ablynx, Belgium). (B) Aggregated Abeta in the soluble brain fraction and (C) Aggregated Abeta measured in 5 µl CSF samples, of APP-London mice of different ages, both in pre-plaque (indicated by the dashed line) and post-plaque stages of the Alzheimer pathology (A4-assay, Amorfix Life Sciences Ltd., Mississauga, Canada). The signal of corresponding non-transgenic mice was under the S/N cut-off value (data not shown).
Reference: Fukumoto H, Tokuda T, Kasai T, Ishigami N, Hidaka H, Kondo M, Allsop D, Nakagawa M. High-molecular-weight beta-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients. FASEB J. 24(8):2716-26 (2010). Pubmed Abstract, Free full text article.
Dr. An Tanghe, Manager Contract Research.
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