Heterogeneous distribution of pathology in behavioral variant Alzheimer’s disease

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AbstractBackgroundA distinct subset of patients with Alzheimer’s disease (AD) experience early and predominant behavioral and personality changes, while the neurobiological origins of these symptoms are largely unknown. In this study, we examined the distribution of tau pathology using PET imaging or post‐mortem evaluation in patients with the behavioral variant of AD (bvAD).MethodFor the PET study, seven amyloid‐β positive clinically diagnosed patients with bvAD from the Amsterdam Dementia Cohort (ADC, n=2), University of California San Francisco (UCSF, n=3) and the Swedish BioFINDER study (n=2) underwent [18F]flortaucipir or [18F]RO948 (tau) PET (Table 1). Regional standardized uptake value ratios (SUVR) in entorhinal, temporoparietal, frontal, and insular cortex as well as mean cortical SUVR and frontal‐to‐parietal SUVR ratios were contrasted against patients with typical (memory‐predominant) AD (tAD; n=55, n=60 and n=90, respectively). For the post‐mortem component of the study, the percentages of AT8 (tau)‐positive areas in hippocampus CA1, temporal, parietal, frontal and insular cortices were compared between 9 cases with bvAD and 7 with tAD.ResultVisual inspection of subject‐specific tau PET patterns revealed more pronounced frontal involvement in 6/7 bvAD patients compared to patients with tAD (Figure 1). Regional SUVR analyses revealed higher‐than‐average tau uptake in 3/7 bvAD cases in the temporoparietal cortex, 5/7 in the frontal cortex, and 3/7 in the insular cortex compared to patients with tAD (Figure 2). Furthermore, 4/7 cases showed higher‐than‐average mean cortical SUVR and 6/7 cases had higher‐than‐average frontal‐to‐parietal SUVR ratios (Figure 2 & Table 2). Postmortem evaluation revealed that bvAD cases had a lower tau load in the CA1 region of the hippocampus compared to patients with tAD (p<.05); no differences were found, however, in temporal, parietal, frontal or insular regions (all p>.05, Figure 3 & Table 3).ConclusionThis multicenter case series with tau PET and neuropathological examination demonstrates a heterogeneous distribution of tau pathology across patients with bvAD, ranging from pronounced anterior involvement to a more temporoparietal pattern. Further work is needed to explore alternative pathophysiological mechanisms underlying the bvAD phenotype.