Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE

Alzheimer's Disease Neuroimaging Initiative

doi:10.1038/ncomms7760

Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE

Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journal › Article › peer-review

258 Scopus citations

Abstract

Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ε4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ε4 being the major genetic risk factor for AD.

Original language	English
Article number	6760
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7760
State	Published - May 19 2015

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10.1038/ncomms7760

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@article{4d62ac3927d0406db2fc8c9e9bb8123f,

title = "Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE",

abstract = "Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ε4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ε4 being the major genetic risk factor for AD.",

author = "{Alzheimer's Disease Neuroimaging Initiative} and Scott Ayton and Faux, {Noel G.} and Bush, {Ashley I.} and Weiner, {Michael W.} and Paul Aisen and Ronald Petersen and Jack, {Clifford R.} and William Jagust and Trojanowki, {John Q.} and Toga, {Arthur W.} and Laurel Beckett and Green, {Robert C.} and Saykin, {Andrew J.} and John Morris and Shaw, {Leslie M.} and Zaven Khachaturian and Greg Sorensen and Lew Kuller and Marc Raichle and Steven Paul and Peter Davies and Howard Fillit and Franz Hefti and Davie Holtzman and Mesulam, {M. Marcel} and William Potter and Peter Snyder and Adam Schwartz and Tom Montine and Thomas, {Ronald G.} and Michael Donohue and Sarah Walter and Devon Gessert and Tamie Sather and Gus Jiminez and Danielle Harvey and Matthew Bernstein and Nick Fox and Paul Thompson and Norbert Schuff and Bret Borowski and Jeff Gunter and Matt Senjem and Prashanthi Vemuri and David Jones and Kejal Kantarci and Chad Ward and Koeppe, {Robert A.} and Beau Ances and Kyle Womack",

year = "2015",

month = may,

day = "19",

doi = "10.1038/ncomms7760",

language = "English",

volume = "6",

journal = "Nature communications",

issn = "2041-1723",

}

TY - JOUR

T1 - Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE

AU - Alzheimer's Disease Neuroimaging Initiative

AU - Ayton, Scott

AU - Faux, Noel G.

AU - Bush, Ashley I.

AU - Weiner, Michael W.

AU - Aisen, Paul

AU - Petersen, Ronald

AU - Jack, Clifford R.

AU - Jagust, William

AU - Trojanowki, John Q.

AU - Toga, Arthur W.

AU - Beckett, Laurel

AU - Green, Robert C.

AU - Saykin, Andrew J.

AU - Morris, John

AU - Shaw, Leslie M.

AU - Khachaturian, Zaven

AU - Sorensen, Greg

AU - Kuller, Lew

AU - Raichle, Marc

AU - Paul, Steven

AU - Davies, Peter

AU - Fillit, Howard

AU - Hefti, Franz

AU - Holtzman, Davie

AU - Mesulam, M. Marcel

AU - Potter, William

AU - Snyder, Peter

AU - Schwartz, Adam

AU - Montine, Tom

AU - Thomas, Ronald G.

AU - Donohue, Michael

AU - Walter, Sarah

AU - Gessert, Devon

AU - Sather, Tamie

AU - Jiminez, Gus

AU - Harvey, Danielle

AU - Bernstein, Matthew

AU - Fox, Nick

AU - Thompson, Paul

AU - Schuff, Norbert

AU - Borowski, Bret

AU - Gunter, Jeff

AU - Senjem, Matt

AU - Vemuri, Prashanthi

AU - Jones, David

AU - Kantarci, Kejal

AU - Ward, Chad

AU - Koeppe, Robert A.

AU - Ances, Beau

AU - Womack, Kyle

PY - 2015/5/19

Y1 - 2015/5/19

N2 - Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ε4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ε4 being the major genetic risk factor for AD.

AB - Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ε4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ε4 being the major genetic risk factor for AD.

UR - http://www.scopus.com/inward/record.url?scp=84930225631&partnerID=8YFLogxK

U2 - 10.1038/ncomms7760

DO - 10.1038/ncomms7760

M3 - Article

C2 - 25988319

AN - SCOPUS:84930225631

SN - 2041-1723

VL - 6

JO - Nature communications

JF - Nature communications

M1 - 6760

ER -

Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE

Abstract

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