Authors: Raphael de Luca e Tuma, Roberta Diehl Rodriguez, Sonia Maria Dozzi Brucki, Claudia Kimie Suemoto, Renata Elaine Paraizo Leite, Renata Eloah de Lucena Ferretti‐Rebustini, Wilson Jacob‐Filho, Carlos Augusto Pasquallucci, Lea Tenenholz Grinberg, Ricardo Nitrini
Published: 2020-12-07
DOI: 10.1002/alz.041186
Source: Full article
AbstractBackgroundThe cerebellum has not been extensively studied in the setting of Alzheimer’s disease (AD). As the disease progresses, the cerebellum is one of the last brain regions to accumulate β‐amyloid (βA) deposits usually as diffuse plaques. However, distinct morphologies are described in the cerebellum in early‐onset Alzheimer’s disease (EOAD).MethodTo investigate the presence of βA deposits in the cerebellum, we analyzed brain sections immunostained with βA antibody (4G8) of 46 individuals with cognitive impairment and neuropathological diagnosis of AD. Of them, cerebellum sections of 19 individuals with Thal phase 5 were evaluated regarding the distribution and morphology of the βA deposits. All cases are from the Biobank for Aging studies of the University of São Paulo. AD‐type pathology was scored using the Braak and Braak staging, CERAD criteria and the Thal phase system. Diagnosis of AD required at least intermediate AD neuropathological changes. Presence of cognitive impairment (CI) was evaluated according to the Clinical Dementia Rating Scale (CDR>0,5).ResultCerebellar βA pathology was found in 19 cases (41%). Higher frequency of amyloid pathology was observed in the group of individuals who developed CI before 65 years of age (87%). In this group of individuals, focal deposits such as compact plaques were more frequently observed than the typical diffuse deposits often seen in molecular layer. Additionally, EOAD individuals had more involvement of Purkinje cell, and granular cell layers than in the molecular layer. Amyloid angiopathy with capillary involvement was observed in the cerebellum of 3 individuals. Of them, only one had EOAD, but all had two APOE ε4 genes.ConclusionThe βA cerebellar involvement can be influenced by the patient’s age, particularly in EOAD cases. These changes observed in the cerebellum may reflect a different vulnerability pattern of βA pathology in individuals with early‐onset AD.