Severity of tauopathy differs between logopenic variant primary progressive aphasia individuals with or without a history of learning differences

ABSTRACT OBJECTIVE To assess differences in the severity of Alzheimer’s disease neuropathological changes in disease epicenters of patients with logopenic variant PPA (lvPPA) with a history of learning differences/developmental dyslexia (LD) versus lvPPA patients without such history (non-LD). BACKGROUND Learning differences, including developmental dyslexia, are overrepresented in the lvPPA population. It is not known whether a history of developmental differences is associated with a more severe phenotypic expression of Alzheimer’s disease pathology. DESIGN/METHODS We quantified the cortical area fraction of phospho-tau immunohistochemistry (IHC) and beta-amyloid IHC in the angular gyrus and superior temporal gyrus of postmortem brains of 15 cases of lvPPA secondary to Alzheimer’s disease of which 9 non-LD cases (2 males and 7 females), and 6 LD cases (2 males and 4 females). Histological sections were digitally acquired, and foreground IHC-signal was automatically separated and thresholded to quantify the respective tau and beta-amyloid area fractions in each region. RESULTS There were no differences in the mean age at death between the two groups. Disease duration was longer in the LD group (10.7 ± 1.2 years) than in the non-LD group (8.1 ± 0.8 years), p =0.09. When corrected for sex, age at death and Apo E4 carrier status, the LD group showed higher tau pathology burden in the superior temporal gyrus compared to the non-LD group (0.91% ± 0.37, p =0.03). No differences in tau pathology burden between the groups were observed in the angular gyrus (0.39% ± 0.41, p =0.37). There were no statistically significant differences in the area fraction of beta-amyloid between the two groups of patients in both the angular gyrus and the superior temporal gyrus. CONCLUSIONS Our data suggest that patients with lvPPA secondary to Alzheimer’s disease and a history of developmental differences have higher tau-pathology burden in the superior temporal gyrus compared to lvPPA-AD patients without such history.