Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry

Abstract

Assessment of Alzheimer’s disease (AD)-related neurofibrillary pathology requires a procedure that permits a sufficient differentiation between initial, intermediate, and late stages. The gradual deposition of a hyperphosphorylated tau protein within select neuronal types in specific nuclei or areas is central to the disease process. The staging of AD-related neurofibrillary pathology originally described in 1991 was performed on unconventionally thick sections (100 μm) using a modern silver technique and reflected the progress of the disease process based chiefly on the topographic expansion of the lesions. To better meet the demands of routine laboratories this procedure is revised here by adapting tissue selection and processing to the needs of paraffin-embedded sections (5–15 μm) and by introducing a robust immunoreaction (AT8) for hyperphosphorylated tau protein that can be processed on an automated basis. It is anticipated that this revised methodological protocol will enable a more uniform application of the staging procedure.

Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer's hippocampus from normal controls

“…Tau‐IP levels of 3 proteins showed nominally significant associations with postmortem interval (PMI), and levels of 4 proteins covaried with age (close to the frequencies expected by chance). In contrast, AD severity based on immunohistochemical features (Braak et al ., 2006) was significantly linked to aggregate tau‐IP levels of 13 proteins (18%) after adjustment for age and PMI effects—substantially more frequently than expected by chance.…”

Impact of tau and amyloid burden on glucose metabolism in Alzheimer's disease

“…The lack of a significant relationship between the pattern of tau pathology and hypometabolism in the hippocampus, an early site of tangles deposition in AD15 is – at least at first sight – somewhat surprising. Consistent with the literature,16, 17 we found moderate levels of hypometabolism in the hippocampus of AD patients, while hippocampal tau deposition did not differ from normal age‐matched controls.…”

Decreased plasma C‐reactive protein levels in APOE ε4 allele carriers

“…In brief, temporal cortical samples were obtained from 71 individuals (18 males and 53 females; mean age, 81.0 ± 8.8 years) examined in Kuopio University Hospital (KUH). The extent of AD‐related neurofibrillary pathology was evaluated after autopsy with AT8‐immunostaining, detecting hyperphosphorylated tau 24. The samples were divided into three groups based on the degree of the neurofibrillary pathology according to Braak staging24: Mild (Braak 0‐II, RNA n = 18/10 and protein n = 8/4 in APOE ε 4 − / ε 4 + , respectively), moderate (Braak III–IV, RNA n = 4/9 and protein n = 3/3 in APOE ε 4 − / ε 4 + , respectively), and severe (Braak V–VI, RNA n = 2/17 and protein n = 2/16 in APOE ε 4 − / ε 4 + , respectively).…”

“…The extent of AD‐related neurofibrillary pathology was evaluated after autopsy with AT8‐immunostaining, detecting hyperphosphorylated tau 24. The samples were divided into three groups based on the degree of the neurofibrillary pathology according to Braak staging24: Mild (Braak 0‐II, RNA n = 18/10 and protein n = 8/4 in APOE ε 4 − / ε 4 + , respectively), moderate (Braak III–IV, RNA n = 4/9 and protein n = 3/3 in APOE ε 4 − / ε 4 + , respectively), and severe (Braak V–VI, RNA n = 2/17 and protein n = 2/16 in APOE ε 4 − / ε 4 + , respectively). The study was approved by the Ethics Committee of the Kuopio University Hospital, University of Eastern Finland, the Finnish National Supervisory Authority, and the Finnish Ministry of Social Affairs and Health.…”