Postmortem T2*- Weighted MRI Imaging of Cortical Iron Reflects Severity of Alzheimer's Disease

Overview

Journal J Alzheimers Dis

Publisher Sage Publications

Specialties Geriatrics
Neurology

Date 2018 Aug 15

PMID 30103327

Citations 30

Authors

Marjolein Bulk

Boyd Kenkhuis

Linda M van der Graaf

Jelle J Goeman

Remco Natte

Louise van der Weerd

Affiliations

Soon will be listed here.

Abstract

The value of iron-based MRI changes for the diagnosis and staging of Alzheimer's disease (AD) depends on an association between cortical iron accumulation and AD pathology. Therefore, this study determined the cortical distribution pattern of MRI contrast changes in cortical regions selected based on the known distribution pattern of tau pathology and investigated whether MRI contrast changes reflect the underlying AD pathology in the different lobes. T2*-weighted MRI was performed on postmortem cortical tissue of controls, late-onset AD (LOAD), and early-onset AD (EOAD) followed by histology and correlation analyses. Combining ex vivo high-resolution MRI and histopathology revealed that: 1) LOAD and EOAD have a different distribution pattern of AD pathological hallmarks and MRI contrast changes over the cortex, with EOAD showing more severe MRI changes; 2) per lobe, severity of AD pathological hallmarks correlates with iron accumulation, and hence with MRI. Therefore, iron-sensitive MRI sequences allow detection of the cortical distribution pattern of AD pathology ex vivo.

Citing Articles

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References

Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K . Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006; 112(4):389-404. PMC: 3906709. DOI: 10.1007/s00401-006-0127-z. View

Alafuzoff I, Arzberger T, Al-Sarraj S, Bodi I, Bogdanovic N, Braak H . Staging of neurofibrillary pathology in Alzheimer's disease: a study of the BrainNet Europe Consortium. Brain Pathol. 2008; 18(4):484-96. PMC: 2659377. DOI: 10.1111/j.1750-3639.2008.00147.x. View

van Duijn S, Nabuurs R, van Rooden S, Maat-Schieman M, van Duinen S, van Buchem M . MRI artifacts in human brain tissue after prolonged formalin storage. Magn Reson Med. 2011; 65(6):1750-8. DOI: 10.1002/mrm.22758. View

Frisoni G, Pievani M, Testa C, Sabattoli F, Bresciani L, Bonetti M . The topography of grey matter involvement in early and late onset Alzheimer's disease. Brain. 2007; 130(Pt 3):720-30. DOI: 10.1093/brain/awl377. View

Peters D, Connor J, Meadowcroft M . The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer's disease: Two sides of the same coin. Neurobiol Dis. 2015; 81:49-65. PMC: 4672943. DOI: 10.1016/j.nbd.2015.08.007. View

Moller C, Vrenken H, Jiskoot L, Versteeg A, Barkhof F, Scheltens P . Different patterns of gray matter atrophy in early- and late-onset Alzheimer's disease. Neurobiol Aging. 2013; 34(8):2014-22. DOI: 10.1016/j.neurobiolaging.2013.02.013. View

Marshall G, Fairbanks L, Tekin S, Vinters H, Cummings J . Early-onset Alzheimer's disease is associated with greater pathologic burden. J Geriatr Psychiatry Neurol. 2007; 20(1):29-33. DOI: 10.1177/0891988706297086. View

Braak H, Braak E, Kalus P . Alzheimer's disease: areal and laminar pathology in the occipital isocortex. Acta Neuropathol. 1989; 77(5):494-506. DOI: 10.1007/BF00687251. View

Koedam E, Lauffer V, van der Vlies A, van der Flier W, Scheltens P, Pijnenburg Y . Early-versus late-onset Alzheimer's disease: more than age alone. J Alzheimers Dis. 2010; 19(4):1401-8. DOI: 10.3233/JAD-2010-1337. View

10.

Langkammer C, Krebs N, Goessler W, Scheurer E, Ebner F, Yen K . Quantitative MR imaging of brain iron: a postmortem validation study. Radiology. 2010; 257(2):455-62. DOI: 10.1148/radiol.10100495. View

11.

Bulk M, Abdelmoula W, Nabuurs R, van der Graaf L, Mulders C, Mulder A . Postmortem MRI and histology demonstrate differential iron accumulation and cortical myelin organization in early- and late-onset Alzheimer's disease. Neurobiol Aging. 2017; 62:231-242. DOI: 10.1016/j.neurobiolaging.2017.10.017. View

12.

Lei P, Ayton S, Finkelstein D, Spoerri L, Ciccotosto G, Wright D . Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat Med. 2012; 18(2):291-5. DOI: 10.1038/nm.2613. View

13.

Ayton S, Faux N, Bush A . Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE. Nat Commun. 2015; 6:6760. PMC: 4479012. DOI: 10.1038/ncomms7760. View

14.

Ward R, Zucca F, Duyn J, Crichton R, Zecca L . The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol. 2014; 13(10):1045-60. PMC: 5672917. DOI: 10.1016/S1474-4422(14)70117-6. View

15.

Braak H, Braak E . Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991; 82(4):239-59. DOI: 10.1007/BF00308809. View

16.

van Duijn S, Nabuurs R, van Duinen S, Natte R . Comparison of histological techniques to visualize iron in paraffin-embedded brain tissue of patients with Alzheimer's disease. J Histochem Cytochem. 2013; 61(11):785-92. PMC: 3808575. DOI: 10.1369/0022155413501325. View

17.

van Rooden S, Buijs M, van Vliet M, Versluis M, Webb A, Oleksik A . Cortical phase changes measured using 7-T MRI in subjects with subjective cognitive impairment, and their association with cognitive function. NMR Biomed. 2014; 29(9):1289-94. DOI: 10.1002/nbm.3248. View

18.

. 2016 Alzheimer's disease facts and figures. Alzheimers Dement. 2016; 12(4):459-509. DOI: 10.1016/j.jalz.2016.03.001. View

19.

Shepherd T, Thelwall P, Stanisz G, Blackband S . Aldehyde fixative solutions alter the water relaxation and diffusion properties of nervous tissue. Magn Reson Med. 2009; 62(1):26-34. PMC: 3188415. DOI: 10.1002/mrm.21977. View

20.

Hare D, Ayton S, Bush A, Lei P . A delicate balance: Iron metabolism and diseases of the brain. Front Aging Neurosci. 2013; 5:34. PMC: 3715022. DOI: 10.3389/fnagi.2013.00034. View