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Updated: Aug 11, 2025

Full- versus Sub-Regional Quantification of Amyloid-Beta Load on Mouse Brain Sections
Published on: May 19, 2022
The relationship between hippocampal amyloid beta burden and spatial distribution of neurofibrillary degeneration
Jamie M Walker1,2,3, William Goette4, Kurt Farrell1,2,3,5,6
1Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
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.
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