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

E. H. Singleton*, Y. A.L. Pijnenburg, P. Gami-Patel, B.D.C. Boon, F. Bouwman, J. M. Papma, H. Seelaar, P. Scheltens, L. T. Grinberg, S. Spina, A. L. Nana, G. D. Rabinovici, W. W. Seeley, R. Ossenkoppele, A. A. Dijkstra

*Corresponding author for this work

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Abstract

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: 260.4 ± 87.1) and tAD (VENs: 32.0 ± 18.1, p = 1.00, GABRQ-ir pyramidal: 349.8 ± 109.6, p = 0.38) and controls (VENs: 33.5 ± 20.3, p = 1.00, GABRQ-ir pyramidal: 339.4 ± 95.9, p = 0.37). Compared to bvFTD, patients with bvAD showed significantly more GABRQ-ir pyramidal neurons (bvFTD: 140.5 ± 82.658, 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.

Original languageEnglish
Article number11
JournalAlzheimer's Research and Therapy
Volume14
Issue number1
DOIs
Publication statusPublished - 20 Jan 2022

Bibliographical note

Funding Information:
Work at the Alzheimer Center Amsterdam was supported by the Netherlands Organisation for Health Research and Development, ZonMw (70-73305-98-1214 to Rik Ossenkoppele, PI). Research of the Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. Work at the University of California San Francisco was supported by the NIH National Institute on Aging (NIA) grants R01-AG045611 (to G.D.R.) as well as funding for Aging and Dementia Research Center (NIA P30-AG062422) and PPG (NIA P01-AG019724). In addition, work at UCSF is funded by K24AG053435 to LTG and KO8 AG052648 to SS.

Publisher Copyright:
© 2022, The Author(s).

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