MR microscopy of human amyloid-ß deposits: characterization of parenchymal amyloid, diffuse plaques, and vascular amyloid.

ABSTRACT

Cerebral deposits of amyloid-ß peptides (Aß) form the neuropathological hallmarks of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). In the brain, Aß can aggregate as insoluble fibrils present in amyloid plaques and vascular amyloid, or as diffuse plaques consisting of mainly non-fibrillar Aß. Previously, magnetic resonance imaging (MRI) has been shown to be capable of detecting individual amyloid plaques, not only via the associated iron, but also Aß 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 Aß deposits including diffuse plaques and vascular amyloid. Postmortem 60-µm-thick brain sections of AD, CAA, and Down's syndrome patients, known to contain Aß, 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 Aß deposit were examined by co-registration of the MRI with Congo Red and Aß-immunostainings of the same sections. Our results show that only fibrillar Aß, 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.