Hyperphosphorylated tau and amyloid-β proteinopathy in people over age 50: Findings from the Lieber Institute for Brain Development Brain Donation Repository

BackgroundThe Lieber Institute for Brain Development (LIBD) has one of the largest postmortem human brain banks for the study of neuropsychiatric disorders in the world. The postmortem evaluation involves neuropathological assessment for age-related protein accumulations, specifically phosphorylated tau (p-tau) and amyloid-β (Aβ).ObjectivePresent the LIBD semiquantitative assessment methodology for p-tau and Aβ by comparing proteinopathy by age and by apolipoprotein E (<i>APOE</i>) genotype.MethodsPostmortem brain tissue samples were from 1509 people aged 50 or greater (median age at death = 63 years; range = 50-102). Seven brain regions (four neocortical areas, hippocampal formation, midbrain, and cerebellum) were examined by routine histopathology, p-tau immunohistochemistry (AT8; hippocampus and four neocortical samples), and Aβ immunohistochemistry (BAM01; four neocortical samples). <i>APOE</i> genotyping was performed in a subgroup. Semiquantitative assessments include modified CERAD (Consortium to Establish a Registry for Alzheimer's Disease) and modified Braak approaches.ResultsThere were 63.8% rated as B1 (modified Braak I or II), 30.4% rated as B2 (modified Braak III or IV), and 5.8% rated as B3 (modified Braak V or VI). For those in their early 70 s, half had modified Braak stage III-IV ratings. For decedents in their 80 s, approximately 1 in 4 had modified Braak stage V-VI ratings. Aβ was present in 48.8% (C0 = 51.2%, C1 = 17.2%, C2 = 24.5%, and C3 = 7.1%). Age and <i>APOE</i> genotype were significant predictors of Aβ plaques.ConclusionsThe LIBD protocol assessing p-tau and Aβ burden identified significant associations with age and <i>APOE</i> genotype. More research is needed to understand the spectrum of age-related proteinopathy versus neurodegenerative disease neuropathology.