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

IntroductionNeurofibrillary 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. MethodsImage analysis-based quantitative pixel assessments were used to objectively evaluate amyloid beta (A beta) burden in the medial temporal lobe in relation to the distribution of hyperphosphorylated-tau (p-tau) in 142 cases of PART and AD. ResultsEntorhinal, CA1, CA3, and CA4 p-tau deposition levels are significantly correlated with A beta burden, while CA2 p-tau is not. Furthermore, the CA2/CA1 p-tau ratio is inversely correlated with A beta burden and distribution. In addition, cognitive impairment is correlated with overall p-tau burden. DiscussionThese data indicate that the presence and extent of medial temporal lobe A beta may determine the distribution and spread of neurofibrillary degeneration. The resulting p-tau distribution patterns may discriminate between PART and AD. HighlightsSubregional 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.

Automated summary

The distribution and spread of neurofibrillary degeneration in Alzheimer's disease (AD) and primary age-related tauopathy (PART) are influenced by the presence and extent of amyloid beta (Aβ) burden in the entorhinal cortex and CA1 subregion of the hippocampus. However, there is an early selective vulnerability of the CA2 subregion in PART, which is not correlated with Aβ burden.