CSF ferritin in the clinicopathological progression of Alzheimer’s disease and associations with APOE and inflammation biomarkers
Year: 2022
Type: article
Study design: Observational Study
Abstract: Background A putative role for iron in driving Alzheimer’s disease (AD) progression is complicated by previously reported associations with neuroinflammation, apolipoprotein E and AD proteinopathy. To establish how iron interacts with clinicopathological features of AD and at what disease stage iron influences cognitive outcomes, we investigated the association of cerebrospinal fluid (CSF) biomarkers of iron (ferritin), inflammation (acute phase response proteins) and apolipoproteins with pathological biomarkers (CSF Aβ42/t-tau, p-tau181), clinical staging and longitudinal cognitive deterioration in subjects from the BioFINDER cohort, with replication of key results in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Methods Ferritin, acute phase response proteins (n=9) and apolipoproteins (n=6) were measured in CSF samples from BioFINDER (n=1239; 4 years cognitive follow-up) participants stratified by cognitive status (cognitively unimpaired, mild cognitive impairment, AD) and for the presence of amyloid and tangle pathology using CSF Aβ42/t-tau (A+) and p-tau181 (T+). The ferritin and apolipoprotein E associations were replicated in the ADNI (n=264) cohort. Results In both cohorts, ferritin and apoE were elevated in A-T+ and A+T+ subjects (16%–40%), but not clinical diagnosis. Other apolipoproteins and acute phase response proteins increased with clinical diagnosis, not pathology. CSF ferritin was positively associated with p-tau181, which was mediated by apolipoprotein E. An optimised threshold of ferritin predicted cognitive deterioration in mild cognitive impairment subjects in the BioFINDER cohort, especially those people classified as A-T- and A+T-. Conclusions CSF markers of iron and neuroinflammation have distinct associations with disease stages, while iron may be more intimately associated with apolipoprotein E and tau pathology.
Authors: Scott Ayton, Shorena Janelidze, Pawel Kalinowski, Sebastian Palmqvist, Abdel Ali Belaidi, Erik Stomrud, Anne Roberts, Blaine Roberts, Oskar Hansson, Ashley Ian Bush
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: U.S. Department of Defense, Foundation for the National Institutes of Health, Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Eli Lilly and Company, Pfizer, Merck, Roche, BioClinica, Novartis Pharmaceuticals Corporation, Takeda Pharmaceutical Company, State Government of Victoria, Innogenetics, Servier, National Institutes of Health, Genentech, Johnson and Johnson, GE Healthcare, National Institute on Aging, Janssen Biotech
Awards: G104586243, G1082030533, G120165940, G2957681590, G3705772492, EFFECTS OF TRAUMATIC BRAIN INJURY (TBI) AND POST TRAUMATIC STRESS DISORDER (PTSD) ON ALZHEIMER'S DISEASE (AD) IN VETERANS USING IMAGING AND BIOMARKERS IN THE AD NEUROIMAGING INITIATIVE (ADNI)", Alzheimer's Disease Neuroimaging Initiative, G9000039018, Alzheimer's Disease Neuroimaging Initiative (ADNI4)
OpenAlex ID: W4308708692