Heterogeneous distribution of tau pathology in the behavioural variant of Alzheimer's disease.

The clinical phenotype of the rare behavioural variant of Alzheimer's disease (bvAD) is insufficiently understood. Given the strong clinico-anatomical correlations of tau pathology in AD, we investigated the distribution of tau deposits in bvAD, in-vivo and ex-vivo, using positron emission tomography (PET) and postmortem examination. For the tau PET study, seven amyloid-β positive bvAD patients underwent [ Individual regional W-scores ≥1.96 (corresponding to p<0.05) were observed in three cases, that is, case #5: medial prefrontal cortex (W=2.13) and anterior default mode network (W=3.79), case #2: lateral prefrontal cortex (W=2.79) and salience network (W=2.77), and case #7: frontal-to-entorhinal ratio (W=2.04). The remaining four cases fell within the normal distributions of the tAD group. Postmortem AT8 staining indicated no group-level regional differences in phosphorylated tau levels between bvAD and tAD (all p>0.05). Both in-vivo and ex-vivo, patients with bvAD showed heterogeneous distributions of tau pathology. Since key regions involved in behavioural regulation were not consistently disproportionally affected by tau pathology, other factors are more likely driving the clinical phenotype in bvAD.

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© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

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Competing interests: OH has acquired research support (for the institution) from Roche, Pfizer, GE Healthcare, Biogen, Eli Lilly and AVID Radiopharmaceuticals. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Biogen and Roche. GDR reports research support from Avid Radiopharmaceuticals, GE Healthcare, Eli Lilly, Life Molecular Imaging; Scientific advisory boards for Axon Neurosciences, Eiasi, Merck, Roche; Associate Editor for JAMA Neurology. PS serves/has served on the advisory boards of: Genentech, Novartis, Pfizer, Roche, Danone, Nutricia, Jansen AI, Baxter and Lundbeck. He has been a speaker at symposia organised by Lundbeck, Lilly, Merz, Pfizer, Jansen AI, Danone, Novartis, Roche and Genentech. He serves on the editorial board of Alzheimer’s Research & Therapy and Alzheimer. Disease and Associated Disorders and is a member of the scientific advisory board of the EU Joint Programming Initiative and the French National Plan Alzheimer. The Alzheimer Center receives unrestricted funding from various sources through the VUmc Fonds. He receives no personal compensation for the activities mentioned above.