BACKGROUND/ OBJECTIVE: The lowering of natively analyzed Abeta42 in cerebrospinal fluid (CSF) is used as a diagnostic tool in Alzheimer's disease (AD). The presence of Abeta oligomers can interfere with such analyses causing underestimation of Abeta levels due to epitope masking. The aim was to investigate if the lowering of CSF Abeta42 seen in AD is caused by oligomerization. METHODS: Abeta42 was analyzed under both denaturing and non-denaturing conditions. An Abeta42 oligomer ratio was calculated from these quantifications. The presence of oligomers leads to Abeta42 epitope masking during non-denaturing assays, resulting in a higher ratio. RESULTS: The Abeta42 oligomer ratio was used for the assessment of oligomerized Abeta in human CSF, after being evaluated in transgenic mouse brain homogenates. AD and mild cognitive impairment (MCI) samples displayed the expected decrease in natively measured Abeta42 compared to healthy controls and frontotemporal dementia, but not when analyzing under denaturing conditions. Accordingly, AD and MCI CSF had a higher Abeta42 oligomer ratio in CSF. CONCLUSION: Combining denaturing and non-denaturing quantifications of Abeta42 into an oligomer ratio enables the assessment of Abeta oligomers in biological samples. The increased Abeta42 oligomer ratio for AD and MCI indicates the presence of oligomers in CSF and that the lowering of natively measured Abeta42 is caused by oligomerization.
BACKGROUND/ OBJECTIVE: The lowering of natively analyzed Abeta42 in cerebrospinal fluid (CSF) is used as a diagnostic tool in Alzheimer's disease (AD). The presence of Abeta oligomers can interfere with such analyses causing underestimation of Abeta levels due to epitope masking. The aim was to investigate if the lowering of CSF Abeta42 seen in AD is caused by oligomerization. METHODS: Abeta42 was analyzed under both denaturing and non-denaturing conditions. An Abeta42 oligomer ratio was calculated from these quantifications. The presence of oligomers leads to Abeta42 epitope masking during non-denaturing assays, resulting in a higher ratio. RESULTS: The Abeta42 oligomer ratio was used for the assessment of oligomerized Abeta in human CSF, after being evaluated in transgenic mouse brain homogenates. AD and mild cognitive impairment (MCI) samples displayed the expected decrease in natively measured Abeta42 compared to healthy controls and frontotemporal dementia, but not when analyzing under denaturing conditions. Accordingly, AD and MCI CSF had a higher Abeta42 oligomer ratio in CSF. CONCLUSION: Combining denaturing and non-denaturing quantifications of Abeta42 into an oligomer ratio enables the assessment of Abeta oligomers in biological samples. The increased Abeta42 oligomer ratio for AD and MCI indicates the presence of oligomers in CSF and that the lowering of natively measured Abeta42 is caused by oligomerization.
Authors: Robert Nisticò; Francesco Mori; Marco Feligioni; Ferdinando Nicoletti; Diego Centonze Journal: Philos Trans R Soc Lond B Biol Sci Date: 2013-12-02 Impact factor: 6.237
Authors: Nunzio Pomara; Davide Bruno; Ricardo S Osorio; Chelsea Reichert; Jay Nierenberg; Antero S Sarreal; Raymundo T Hernando; Charles R Marmar; Thomas Wisniewski; Henrik Zetterberg; Kaj Blennow Journal: Neuroreport Date: 2016-09-28 Impact factor: 1.837
Authors: Edmond Teng; Karen Taylor; Tina Bilousova; David Weiland; Thaidan Pham; Xiaohong Zuo; Fusheng Yang; Ping-Ping Chen; Charles G Glabe; Alison Takacs; Dennis R Hoffman; Sally A Frautschy; Gregory M Cole Journal: Neurobiol Dis Date: 2015-09-12 Impact factor: 5.996
Authors: John M Ringman; Jennifer L Tomic; Giovanni Coppola; David Elashoff; Karen H Gylys; Charles G Glabe Journal: Dement Geriatr Cogn Dis Extra Date: 2012-12-15