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

Cerebral deposits of amyloid-beta peptides (A beta) form the neuropathological hallmarks of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). In the brain, A beta can aggregate as insoluble fibrils present in amyloid plaques and vascular amyloid, or as diffuse plaques consisting of mainly non-fibrillar A beta. Previously, magnetic resonance imaging (MRI) has been shown to be capable of detecting individual amyloid plaques, not only via the associated iron, but also A beta 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 A beta deposits including diffuse plaques and vascular amyloid. Postmortem 60-mu m-thick brain sections of AD, CAA, and Down's syndrome patients, known to contain A beta, were studied. High resolution T-2* - and T-2-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 A beta deposit were examined by co-registration of the MRI with Congo Red and A beta-immunostainings of the same sections. Our results show that only fibrillar A beta, present in both vascular and parenchymal amyloid, induced a significant change in T-2* and T-2 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.