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MR Microscopy of Human Amyloid-β Deposits: Characterization of Parenchymal Amyloid, Diffuse Plaques, and Vascular Amyloid

Article type: Research Article

Authors: Nabuurs, Rob J.A.a; * | Natté, Remcob | de Ronde, Fenna M.a | Hegeman-Kleinn, Ingrida; b; c | Dijkstra, Jouked | van Duinen, Sjoerd G.b | Webb, Andrew G.a | Rozemuller, Annemieke J.e | van Buchem, Mark A.a | van der Weerd, Louisea; f; g

Affiliations: [a] Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands | [b] Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands | [c] Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands | [d] Division of Image Processing (LKEB), Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands | [e] Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands | [f] Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands | [g] Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

Correspondence: [*] Correspondence to: Rob J.A. Nabuurs, M.Sc., Department of Radiology C2S, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Tel.: +31 71 5264376; Fax: +31 71 5248256; E-mail: [email protected].

Keywords: Alzheimer's disease, amyloid-β, amyloid plaque, cerebral amyloid angiopathy, magnetic resonance imaging

DOI: 10.3233/JAD-122215

Journal: Journal of Alzheimer's Disease, vol. 34, no. 4, pp. 1037-1049, 2013

Accepted 24 December 2012
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Published: 20 March 2013
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Abstract

Cerebral deposits of amyloid-β peptides (Aβ) form the neuropathological hallmarks of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). In the brain, Aβ can aggregate as insoluble fibrils present in amyloid plaques and vascular amyloid, or as diffuse plaques consisting of mainly non-fibrillar Aβ. Previously, magnetic resonance imaging (MRI) has been shown to be capable of detecting individual amyloid plaques, not only via the associated iron, but also Aβ itself has been suggested to be responsible for a decrease in the image intensity. In this current study we aim to investigate the MRI properties of the different cerebral Aβ deposits including diffuse plaques and vascular amyloid. Postmortem 60-μm-thick brain sections of AD, CAA, and Down's syndrome patients, known to contain Aβ, were studied. High resolution T2*- and T2-weighted MRI scans and quantitative relaxation maps were acquired using a microcoil on a Bruker 9.4T MRI system. Specific MRI characteristics of each type of Aβ deposit were examined by co-registration of the MRI with Congo Red and Aβ-immunostainings of the same sections. Our results show that only fibrillar Aβ, present in both vascular and parenchymal amyloid, induced a significant change in T2* and T2 values. However, signal changes were not as consistent for all of the vessels affected by CAA, irrespective of possible dyshoric changes. In contrast, the non-fibrillar diffuse plaques did not create any detectable MRI signal changes. These findings are relevant for the interpretation and further development of (quantitative) MRI methods for the detection and follow-up of AD and CAA.

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