AbstractBackgroundEarly onset sporadic Alzheimer’s disease (AD) sometimes presents with non‐memory symptoms attributed to relatively greater neocortical than hippocampal tau neurofibrillary tangle (NFT) density. Posterior cortical atrophy (PCA) is a variant of AD presenting with visuospatial deficits and atrophy of the occipital cortex, yet the pathologic underpinning is poorly understood.MethodWe examined brains of 50 patients with early onset (age<65 y.), autopsy‐confirmed AD from the UCSD Alzheimer’s Disease Research Center, 12 of whom were clinically diagnosed with PCA. Immunohistochemistry for tau was performed in the hippocampus (HP), midfrontal cortex (MF), and occipital cortex (OC), and the density of NFTs was measured.ResultPCA and non‐PCA patients did not significantly differ in age (63.35±4.59 y. at death) or sex (40% female). The APOE ε4 allele was much less frequent in PCA (p = 0.002). While the PCA group was less impaired on the MMSE (p = 0.01), they performed comparably on the CDR sum‐of‐boxes. The OC NFT density did not differ between the groups; however, the OC/HP (p = 0.04) and OC/MF (p = 0.008) ratios demonstrate that PCA cases had relatively greater OC pathology than non‐PCA patients. Across the groups, age at symptom onset was inversely associated with OC NFT density (p = 0.01) and the OC/HP NFT ratio (p = 0.008), such that earlier onset was associated with greater OC NFT burden. Visuospatial performance, measured by the Block Design test, was associated with the OC NFT density (p = 0.006), as well as the OC/HP (p = 0.007) and OC/MF NFT ratios (p = 0.03), with the effects remaining significant when restricting to non‐PCA participants. In contrast, memory performance measured by the Logical Memory Immediate Recall measure was only associated with HP NFT density (p = 0.02).ConclusionDespite differences in the predominance of early visuospatial symptoms, PCA and non‐PCA patients did not differ in OC tangle density, with some of the highest densities in non‐PCA patients. However, the degree of visuospatial impairment was associated with the OC/HP NFT ratio across both groups. Results suggest that greater memory impairment in the non‐PCA patients associated with a higher HP tangle density may moderate the predominance of visuospatial impairment so that they do not receive a formal PCA diagnosis.