Amyloid plaques associated with shift in patterns of hippocampal tau pathology in middle age.

BackgroundTau pathology begins to accumulate in the medial temporal lobe in many individuals in middle age. Some individuals develop amyloid pathology, more advanced tau pathology (Braak stage), and higher levels of CA1 hippocampal tau pathology in the context of Alzheimer's disease. Others never develop significant amyloid pathology; in these cases, hippocampal tau pathology can be CA2-predominant and tends not to accumulate past intermediate stages. But factors associated with the early formation of these tau patterns is unclear.ObjectiveThe objective of this study is to examine demographic, genetic (APOE), and pathologic factors associated with the emergence of hippocampal tau pathology patterns in middle age.MethodsWe identified 89 individuals with hippocampal tau pathology ages 65 and younger. These cases were assessed for tau stage, amyloid plaques, and APOE4 status. Hippocampal tau pathology in CA1 and CA2 was scored semi-quantitatively.ResultsIn a younger aging population, tau pathology initially deposits at low levels in CA1 and CA2. In the presence of amyloid, tau pathology is increased in both CA1 and CA2, but with a shift toward a greater proportion of cases with higher tau pathology in CA1.ConclusionsPatterns of tau pathology in middle age are strongly associated with amyloid plaques, including increased CA1 and CA2 pathology and a greater proportion of CA1-predominant cases. In the absence of amyloid, tau pathology shows a normal (Gaussian) distribution between CA1 and CA2. These tau pathology distributions at younger ages are similar to the patterns seen at older ages in AD and PART.