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[P2–068]: SOLUBLE AMYLOID‐BETA AGGREGATES FROM HUMAN ALZHEIMER's DISEASE BRAINS
Author(s) -
Esparza Thomas J.,
Wildburger Norelle C.,
Jiang Hao,
Gangolli Mihika,
Bateman Randall J.,
Brody David L.
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.717
Subject(s) - immunoelectron microscopy , chemistry , immunoprecipitation , protein aggregation , ultracentrifuge , differential centrifugation , biophysics , ex vivo , size exclusion chromatography , biochemistry , thioflavin , antibody , in vitro , chromatography , alzheimer's disease , biology , pathology , immunology , enzyme , gene , medicine , disease
during life. We studied the prevalence and topographical distribution of microbleeds and microinfarcts on ex vivo MRI in CAA cases. Moreover, we determined number of microbleeds and microinfarcts on microscopy of standard samples to compare to the numbers detected by MRI. We specifically sought to compare MRI’s methodologic advantage of providing full brain coverage to microscopy’s advantage of greater sensitivity for detection of these two lesion types. Methods:We included four patients with a diagnosis ofCAAduring lifewhodonated their brains toCAAresearch (mean age at death 73.466.7 years). One control case was included from our neuropathology database, a 90-year old individual without cognitive impairment. At autopsy, the brains were removed and formalin-fixed. The hemisphere without macrohemorrhage was packed in a bag with periodate-lysine-paraformaldehyde and scanned overnight at 3T MRI. The protocol included a flash (resolution 500x500x500mm) and a T2-weighted sequence (resolution 500x500x500mm). On the acquired scans, cortical microbleeds and microinfarcts were assessed. In parallel, the hemisphere was cut in 10mm-thick coronal slabs. Subsequently, four pre-defined standard areaswere sampled, blinded toMRI (one area from the frontal, parietal, temporal, and occipital cortex), embedded in paraffin, and cut in 6mmthick sections.One sectionwas stainedwithH&E, and screenedmicroscopically for microbleeds andmicroinfarcts. The adjacent section underwent Ab immunohistochemistry to determine CAA severity. Results: On ex vivoMRI 426 microbleeds [range 39-261] and 313 microinfarcts [range 21-144] were identified in the four CAA cases. Microbleeds and microinfarcts did not spatially overlap on MRI, but showed distinct topographical patterns. Microscopy revealed 3 microbleeds [range 0-2 per case] and 25 microinfarcts [range 0-15 per case] in the 16 examined sections. All cases showed CAA, ranging from mild-to-severe. The control case had3microinfarcts and 0microbleeds onMRI, andmicroscopy revealed no lesions of either type and absence of CAA. Conclusions: In CAA, superior brain coverage provided by MRI resulted in more sensitive microbleed detection. In contrast, MRI appears to substantially undercount microinfarcts, which are often better detectable by themore sensitivemethod of histopathology.