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The behavioral variant of Alzheimer's disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex

By Ellen Singleton, Yolande A.L. Pijnenburg, Priya Gami-Patel, Baayla D.C. Boon, Femke Bouwman, Janne M. Papma, Harro Seelaar, Philip Scheltens, Lea T. Grinberg, Salvatore Spina, Alissa Nana Li, Gil D. Rabinovici, William W Seeley, Rik Ossenkoppele, Anke A. Dijkstra

Posted 30 Oct 2021
medRxiv DOI: 10.1101/2021.10.30.21265649

Background: The neurobiological origins of the early and predominant behavioral changes seen in the behavioral variant of Alzheimer's disease (bvAD) remain unclear. A selective loss of Von Economo Neurons (VENs) and phylogenetically related neurons have been observed in behavioral variant frontotemporal dementia (bvFTD) and several psychiatric diseases. Here, we assessed whether these specific neuronal populations show a selective loss in bvAD. Methods: VENs and GABA receptor subunit theta (GABRQ)-immunoreactive pyramidal neurons of the anterior cingulate cortex (ACC) were quantified in post-mortem tissue of patients with bvAD (n=9) and compared to typical AD (tAD, n=6), bvFTD due to frontotemporal lobar degeneration based on TDP-43 pathology (FTLD, n=18) and controls (n=13) using ANCOVAs adjusted for age and Bonferroni corrected. In addition, ratios of VENs and GABRQ-immunoreactive (GABRQ-ir) pyramidal neurons over all Layer 5 neurons were compared between groups to correct for overall Layer 5 neuronal loss. Results: The number of VENs or GABRQ-ir neurons did not differ significantly between bvAD (VENs: 26.0{+/-}15.3, GABRQ-ir pyramidal: 260.44{+/-}87.13) and tAD (VENs: 32.0{+/-}18.1, p=1.00, GABRQ-ir pyramidal: 349.83{+/-}109.64, p=0.38) and controls (VENs: 33.5{+/-}20.3, p=1.00, GABRQ-ir pyramidal: 339.38{+/-}95.88, p=0.37). Compared to bvFTD, patients with bvAD showed significantly more GABRQ-ir pyramidal neurons (bvFTD: 140.39{+/-}82.58, p=0.01) and no significant differences in number of VENs (bvFTD: 10.9{+/-}13.8, p=0.13). Results were similar when assessing the number of VENs and GABRQ-ir relative to all neurons of Layer 5. Discussion: VENs and phylogenetically related neurons did not show a selective loss in the ACC in patients with bvAD. Our results suggest that, unlike in bvFTD, the clinical presentation in bvAD may not be related to the loss of VENs and related neurons in the ACC.

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