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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
Discrepancies between CSF biomarker and PET determinations of elevated brain amyloid and their prognostic
David S Knopman1, Stephen D Weigand2, Heather J Wiste2
1Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Introduction:
When cerebrospinal fluid (CSF) and positron emission tomography (PET) measurements for amyloid-beta-peptide (Aβ) related pathology are discordant, therapeutic decision-making becomes uncertain.
Methods:
Using data from patients with mild cognitive impairment (n = 541) from the Alzheimer's Disease Neuroimaging Initiative, we examined baseline characteristics and longitudinal clinical outcomes in persons grouped according to normal/abnormal Aβ via concurrent CSF and PET determinations using standard cutpoints.
Results:
Discordant groups for brain Aβ status (CSF+/PET- and CSF-/PET+) each represented about 5% of the mild cognitive impairment (MCI) population. Longitudinally, neither discordant group declined more than the CSF-/PET- group on either a memory measure or the Clinical Dementia Rating Sum of Boxes scores over a median 4 years of observation, while the CSF+/PET+ group exhibited worsening on both measures.
Discussion:
In contrast to the clinical decline observed in the CSF+/PET+ group, persons with MCI and CSF+/PET- or CSF-/PET+ brain amyloid patterns did not exhibit incipient decline.
Highlights:
Discrepant abnormal cerebrospinal fluid (CSF) and positron emission tomography (PET) brain amyloid indicators are uncommon in mild cognitive impairment (MCI). CSF-PET discrepant persons with MCI tend to have less abnormal values initially. CSF-PET discrepant persons with MCI have a benign prognosis at 4 years.
