Anterior MTL Subregions, Especially BA35, Show Early Vulnerability to Tau-Related Neurodegeneration in Alzheimer's Disease

The anterior medial temporal lobe (MTL), including the entorhinal cortex (ERC) and Brodmann area 35 (BA35), is an initial site of tau pathology in Alzheimer's disease (AD). However, standard image segmentation methods often fail to precisely capture these critical regions. This limitation impedes accurate localization and staging of early tau-related neurodegeneration. This study addresses this gap by employing an advanced automated segmentation approach to better characterize early AD pathology using tau-PET and plasma phosphorylated tau 217 (p-tau217).

Researchers utilized an automated segmentation approach with an extended ASHS (Automatic Segmentation of Hippocampal Subfields) atlas to precisely delineate anterior MTL subregions. The study included 448 participants from the Pennsylvania Alzheimer's Disease Research Center. Data collected included magnetic resonance imaging (MRI), tau positron emission tomography (PET) from 199 individuals, and plasma phosphorylated tau 217 (p-tau217) from 377 individuals. Amyloid beta (Aβ) positivity was determined using either PET or plasma measurements, allowing for assessment in cognitively unimpaired Aβ-positive cohorts.

Tau-PET imaging revealed a distinct anterior-posterior gradient of tau pathology, with the highest uptake concentrated in the Brodmann area 35 (BA35), entorhinal cortex (ERC), and anterior hippocampus. > Significantly, elevated MTL tau-PET uptake and higher plasma p-tau217 levels were strongly associated with localized cortical thinning within BA35 and ERC. This critical association was evident even in cognitively unimpaired individuals who were amyloid beta (Aβ)-positive, indicating early structural changes preceding overt cognitive decline. These findings underscore the early vulnerability of these specific anterior MTL subregions to tau-related neurodegeneration.