CSF complement 3 and factor H are staging biomarkers in Alzheimer's disease

Acta Neuropathologica Communications
William T HuAlzheimer’s Disease Neuro-Imaging Initiative

Abstract

CSF levels of established Alzheimer's disease (AD) biomarkers remain stable despite disease progression, and non-amyloid non-tau biomarkers have the potential of informing disease stage and progression. We previously identified complement 3 (C3) to be decreased in AD dementia, but this change was not found by others in earlier AD stages. We hypothesized that levels of C3 and associated factor H (FH) can potentially distinguish between mild cognitive impairment (MCI) and dementia stages of AD, but we also found their levels to be influenced by age and disease status. We developed a biochemical/bioinformatics pipeline to optimize the handling of complex interactions between variables in validating biochemical markers of disease. We used data from the Alzheimer's Disease Neuro-imaging Initiative (ADNI, n = 230) to build parallel machine learning models, and objectively tested the models in a test cohort (n = 73) of MCI and mild AD patients independently recruited from Emory University. Whereas models incorporating age, gender, APOE ε4 status, and CSF amyloid and tau levels failed to reliably distinguish between MCI and mild AD in ADNI, introduction of CSF C3 and FH levels reproducibly improved the distinction between the two AD st...Continue Reading

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Citations

Jul 1, 2016·Acta Neuropathologica Communications·Luke W BonhamUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Nov 4, 2017·Alzheimer's Research & Therapy·Jennifer C HowellWilliam T Hu
Feb 10, 2018·Multiple Sclerosis : Clinical and Laboratory Research·Wioleta M ZelekB Paul Morgan
Aug 24, 2019·Molecular Psychiatry·Julia J WooJames L Kennedy
Sep 27, 2018·Alzheimer's Research & Therapy·Umesh GangishettiWilliam T Hu
Mar 20, 2019·Frontiers in Immunology·Sarah M CarpaniniBryan Paul Morgan
Jun 18, 2020·Frontiers in Neurology·David A Loeffler
May 12, 2020·Frontiers in Immunology·Junling YangKen-Ichiro Fukuchi
Nov 17, 2020·Trends in Neurosciences·Marlene Kanmogne, Robyn S Klein
Jun 30, 2021·Nature Communications·William T HuUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Apr 2, 2021·Dementia and Geriatric Cognitive Disorders Extra·Lynn Marie TrottiWilliam T Hu

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