While the hippocampal cornu ammonis 1 (CA1) subfield is known to be an early site of tau pathology in Alzheimer’s disease (AD), it is unclear how tau pathology in Primary Age Related Tauopathy (PART), defined by the presence of tau-based neurofibrillary tangles in the absence of beta amyloid, relates to subfield structure.

To investigate  relationships between the amount of tau binding measured by AV1451 PET imaging and atrophy within medial temporal lobe (MTL) subregions, as measured by MTL-focused high-resolution structural MRI in individuals classified as either Amyloid-β positive or negative based on Florbetapir-PET imaging.

We studied 188 participants from ADNI across the spectrum of disease stages (114 Amyloid- , 73 Amyloid+). High-resolution T2-MRI was used for making MTL subregional atrophy measurements. ASHS segmentation software produced volumetric measurements of hippocampal subfields and  parahippocampal (PHC), entorhinal (ERC), and perirhinal (PRC) cortices. Regional thickness maps were generated within the MTL cortical ribbon. A summary measure of MTL tau tracer uptake was obtained from ¹⁸F-florbetapir Tau-PET scans. Tracer uptake was correlated with atrophy measures. Intracranial volume, age, and time between MRI and PET scans were used as covariates.

Both ROI and regional thickness analysis revealed strong relationships between atrophy measures and tau tracer uptake. Correlations were strongest within the BA35 region of PRC, approximating transentorhinal cortex, and ERC in both Amyloid- and Amyloid+ subsets. Within the CA fields, regional thickness analysis revealed greater correlation more medially, near CA2 subfield, in Amyloid- , in contrast with CA1 subfield in Amyloid+.

These results represent the first in-vivo evidence of subregion-specific correlations between tau burden and local atrophy in both Amyloid+ and Amyloid- individuals. Strongest effects in BA35, followed by ERC, and CA1 subfield mirror the progression of tau pathology along Braak stages. Stronger  effect near CA2 in Amyloid- supports recent pathological evidence of CA2 tau accummulation in PART.