The relationship between hippocampal amyloid beta burden and spatial distribution of neurofibrillary degeneration

Introduction: Neurofibrillary degeneration in Alzheimer's disease (AD) typically involves the entorhinal cortex and CA1 subregion of the hippocampus early in the disease process, whereas in primary age-related tauopathy (PART), there is an early selective vulnerability of the CA2 subregion. Methods: Image analysis-based quantitative pixel assessments were used to objectively evaluate amyloid beta (Aβ) burden in the medial temporal lobe in relation to the distribution of hyperphosphorylated-tau (p-tau) in 142 cases of PART and AD. Results: Entorhinal, CA1, CA3, and CA4 p-tau deposition levels are significantly correlated with Aβ burden, while CA2 p-tau is not. Furthermore, the CA2/CA1 p-tau ratio is inversely correlated with Aβ burden and distribution. In addition, cognitive impairment is correlated with overall p-tau burden. Discussion: These data indicate that the presence and extent of medial temporal lobe Aβ may determine the distribution and spread of neurofibrillary degeneration. The resulting p-tau distribution patterns may discriminate between PART and AD. Highlights: Subregional hyperphosphorylated-tau (p-tau) distribution is influenced by hippocampal amyloid beta burden. Higher CA2/CA1 p-tau ratio is predictive of primary age-related tauopathy–like neuropathology. Cognitive function is correlated with the overall hippocampal p-tau burden.