Characterization of cerebellar amyloid-β deposits in Alzheimer disease

Cerebellar amyloid-β (Aβ) plaques are a component of the diagnostic criteria used in Thal staging and ABC scoring for Alzheimer disease (AD) neuropathologic change. However, Aβ deposits in this anatomic compartment are unique and under-characterized; and their relationship with other pathological findings are largely undefined. In 73 cases of pure or mixed AD with an A3 score in the ABC criteria, parenchymal (plaques) and vascular (cerebral amyloid angiopathy [CAA]) cerebellar Aβ-42 deposits were characterized with respect to localization, morphology, density, and intensity. Over 85% of cases demonstrated cerebellar Aβ-42 parenchymal staining that correlated with a Braak stage V-VI/B3 score (p < 0.01). Among the 63 with cerebellar Aβ-42 deposits, a diffuse morphology was observed in 75% of cases, compact without a central dense core in 32%, and compact with a central dense core in 16% (all corresponding to plaques evident on hematoxylin and eosin staining). Cases with Purkinje cell (PC) loss showed higher proportions of PC layer Aβ-42 staining than cases without PC loss (88% vs 44%, p = 0.02), suggesting a link between Aβ-42 deposition and PC damage. Among all 73 cases, CAA was observed in the parenchymal vessels of 19% of cases and in leptomeningeal vessels in 44% of cases.