Microbleeds and Cerebral Amyloid Angiopathy in the Brains of People with Down Syndrome with Alzheimer’s Disease

Article type: Research Article

Authors: Helman, Alex M.^{a; b} | Siever, Morgan^b | McCarty, Katie L.^b | Lott, Ira T.^{c; d} | Doran, Eric^c | Abner, Erin L.^{b; e} | Schmitt, Frederick A.^{b; f} | Head, Elizabeth^{b; g; *}

Affiliations: [a] Department of Molecular & Cellular Biochemistry, University of Kentucky, Lexington, KY, USA | [b] Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA | [c] Department of Pediatrics, University of California, Irvine, Irvine, CA, USA | [d] Department of Neurology, University of California, Irvine, Irvine, CA, USA | [e] Department of Epidemiology, University of Kentucky, Lexington, KY, USA | [f] Department of Neurology, University of Kentucky, Lexington, KY, USA | [g] Department of Pharmacology & Nutritional Sciences, University of Kentucky, Lexington, KY, USA

Correspondence: [*] Correspondence to: Elizabeth Head, PhD, Sanders Brown Center on Aging, University of Kentucky, 800 South Limestone Street, Lexington, KY, 40536, USA. E-mail: [email protected].

Abstract: Cerebrovascular pathology is a significant mediator in Alzheimer’s disease (AD) in the general population. In people with Down syndrome (DS), the contribution of vascular pathology to dementia may play a similar role in age of onset and/or the rate of progression of AD. In the current study, we explored the extent of microbleeds (MBs) and the link between cerebral amyloid angiopathy (CAA) and MBs in the frontal cortex (FCTX) and occipital cortex (OCTX) in an autopsy series from individuals with DS (<40 years), DS with AD pathology (DSAD), sporadic AD, and control cases (2–83 years). Sections were immunostained against Aβ1 - 40 and an adjacent section stained using Prussian blue for MBs. MBs were both counted and averaged in each case and CAA was scored based on previously published methods. MBs were more frequent in DS cases relative to controls but present to a similar extent as sporadic AD. This aligned with CAA scores, with more extensive CAA in DS relative to controls in both brain regions. CAA was also more frequent in DSAD cases relative to sporadic AD. We found CAA to be associated with MBs and that MBs increased with age in DS after 30 years of age in the OCTX and after 40 years of age in the FCTX. MB and CAA appear to be a significant contributors to the development of dementia in people with DS and are important targets for future clinical trials.

Keywords: Cerebral amyloid angiopathy, microhemorrhages, Prussian blue, trisomy 21

DOI: 10.3233/JAD-180589

Journal: Journal of Alzheimer's Disease, vol. 67, no. 1, pp. 103-112, 2019