This is a Swedish - Australian study using 2 big cohorts to study the role of ferritin, APOE, and inflammation markers in the progression of AD.

Looks like iron has a role both in APOE and tau pathology. Ayton and Bush, authors of this paper, published in April another paper that indicated APOE possibly inhibits ferroptosis.

Unfortunately, this is not a free paper but here is the abstract:

J Neurol Neurosurg Psychiatry

. 2022 Nov 10;jnnp-2022-330052.

doi: 10.1136/jnnp-2022-330052. Online ahead of print.

CSF ferritin in the clinicopathological progression of Alzheimer's disease and associations with APOE and inflammation biomarkers

Scott Ayton ^{1 2}, Shorena Janelidze ³, Pawel Kalinowski ^{1 2}, Sebastian Palmqvist ^{3 4}, Abdel Ali Belaidi ^{1 2}, Erik Stomrud ^{3 5}, Anne Roberts ⁶, Blaine Roberts ⁶, Oskar Hansson ⁷, Ashley Ian Bush ^{8 2}

Affiliations expand

• PMID: 36357168

DOI: 10.1136/jnnp-2022-330052

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.

Keywords: alzheimer's disease; iron deposition.