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Open Access 01-12-2024 | Frontotemporal Dementia | Research

Phenotypically concordant distribution of pick bodies in aphasic versus behavioral dementias

Authors: Allegra Kawles, Rachel Keszycki, Grace Minogue, Antonia Zouridakis, Ivan Ayala, Nathan Gill, Alyssa Macomber, Vivienne Lubbat, Christina Coventry, Emily Rogalski, Sandra Weintraub, Qinwen Mao, Margaret E. Flanagan, Hui Zhang, Rudolph Castellani, Eileen H. Bigio, M.-Marsel Mesulam, Changiz Geula, Tamar Gefen

Published in: Acta Neuropathologica Communications | Issue 1/2024

Abstract

Pick’s disease (PiD) is a subtype of the tauopathy form of frontotemporal lobar degeneration (FTLD-tau) characterized by intraneuronal 3R-tau inclusions. PiD can underly various dementia syndromes, including primary progressive aphasia (PPA), characterized by an isolated and progressive impairment of language and left-predominant atrophy, and behavioral variant frontotemporal dementia (bvFTD), characterized by progressive dysfunction in personality and bilateral frontotemporal atrophy. In this study, we investigated the neocortical and hippocampal distributions of Pick bodies in bvFTD and PPA to establish clinicopathologic concordance between PiD and the salience of the aphasic versus behavioral phenotype. Eighteen right-handed cases with PiD as the primary pathologic diagnosis were identified from the Northwestern University Alzheimer’s Disease Research Center brain bank (bvFTD, N = 9; PPA, N = 9). Paraffin-embedded sections were stained immunohistochemically with AT8 to visualize Pick bodies, and unbiased stereological analysis was performed in up to six regions bilaterally [middle frontal gyrus (MFG), superior temporal gyrus (STG), inferior parietal lobule (IPL), anterior temporal lobe (ATL), dentate gyrus (DG) and CA1 of the hippocampus], and unilateral occipital cortex (OCC). In bvFTD, peak neocortical densities of Pick bodies were in the MFG, while the ATL was the most affected in PPA. Both the IPL and STG had greater leftward pathology in PPA, with the latter reaching significance (p < 0.01). In bvFTD, Pick body densities were significantly right-asymmetric in the STG (p < 0.05). Hippocampal burden was not clinicopathologically concordant, as both bvFTD and PPA cases demonstrated significant hippocampal pathology compared to neocortical densities (p < 0.0001). Inclusion-to-neuron analyses in a subset of PPA cases confirmed that neurons in the DG are disproportionately burdened with inclusions compared to neocortical areas. Overall, stereological quantitation suggests that the distribution of neocortical Pick body pathology is concordant with salient clinical features unique to PPA vs. bvFTD while raising intriguing questions about the selective vulnerability of the hippocampus to 3R-tauopathies.

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Title: Phenotypically concordant distribution of pick bodies in aphasic versus behavioral dementias
Authors: Allegra Kawles
Rachel Keszycki
Grace Minogue
Antonia Zouridakis
Ivan Ayala
Nathan Gill
Alyssa Macomber
Vivienne Lubbat
Christina Coventry
Emily Rogalski
Sandra Weintraub
Qinwen Mao
Margaret E. Flanagan
Hui Zhang
Rudolph Castellani
Eileen H. Bigio
M.-Marsel Mesulam
Changiz Geula
Tamar Gefen
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Frontotemporal Dementia
Frontotemporal Dementia
Dementia
Dementia
Aphasia
Pathology
Intense Pulsed Light
Alzheimer's Disease
Alzheimer's Disease
Published in: Acta Neuropathologica Communications / Issue 1/2024
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-024-01738-7

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Phenotypically concordant distribution of pick bodies in aphasic versus behavioral dementias

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