Impact of cerebrospinal fluid matrix on the detection of Alzheimer's disease with Aβ42 and influence of disease on the total-Aβ42/Aβ40 ratio

Journal of Neurochemistry
J Randall SlemmonKaj Blennow

Abstract

The 42-amino acid fragment of amyloid β (Aβ1-42) in cerebrospinal fluid has continued to be important for detecting cerebral β-amyloidosis in Alzheimer's disease (AD). However, there are impediments to our ability to fully understand this measurement, including matrix interference and changes linked to apolipoprotein E (APOE) ε4 genotype. This study investigated matrix interference as a contributing factor for detecting AD in APOE ε4-negative patients by comparing total extractable Aβ1-42 to free Aβ1-42. It also examined the ratio of total Aβ1-42 to Aβ1-40, since changes relative to other Aβ peptides may provide a measurement of cerebral β-amyloidosis that is neutral to changes in APP metabolism. Total Aβ1-42 lost the diagnostic power for detecting AD, confirming a role for matrix in the diagnostic. However, when total Aβ1-42/Aβ1-40 was examined, the separation between groups was reestablished. This result was confirmed in a second sample set of unknown APOE status. These results confirmed that matrix interference in some cerebrospinal fluid samples appears to contribute to identifying AD patients and this can be compensated by using a total extracted Aβ1-42/Aβ1-40 ratio when matrix interference is small. It may be preferable t...Continue Reading

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Mar 24, 2017·Molecular Neurobiology·Katarzyna Marta Zoltowska, Oksana Berezovska
Jan 7, 2017·Journal of Alzheimer's Disease : JAD·Jamie ToombsHenrik Zetterberg
May 22, 2018·Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring·Jamie ToombsHenrik Zetterberg
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Jul 21, 2017·Frontiers in Neurology·Linda J C van Waalwijk van DoornCharlotte E Teunissen
Jan 22, 2021·Physiological Reviews·Camilla Ferrari, Sandro Sorbi

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