| Poster | Poster Session 06 Program Schedule
02/15/2024
04:00 pm - 05:15 pm
Room: Majestic Complex (Posters 61-120)
Poster Session 06: Aging | MCI | Neurodegenerative Disease - PART 2
Final Abstract #111
Anatomic Selectivity of Cortical Neuronal and Glial Tau in Behavioral Variant Frontotemporal Dementia with 4R FTLD-tau
Antonia Zouridakis, Northwestern University Feinberg School of Medicine, Chicago, United States
Grace Minogue, Northwestern University Feinberg School of Medicine, Chicago, United States
Allegra Kawles, Northwestern University Feinberg School of Medicine, Chicago, United States
Rachel Keszycki, Northwestern University Feinberg School of Medicine, Chicago, United States
Alyssa Macomber, Northwestern University Feinberg School of Medicine, Chicago, United States
Vivienne Lubbat, Northwestern University Feinberg School of Medicine, Chicago, United States
Nathan Gill, Northwestern University Feinberg School of Medicine, Chicago, United States
Sandra Weintraub, Northwestern University Feinberg School of Medicine, Chicago, United States
Rudolph Castellani, Northwestern University Feinberg School of Medicine, Chicago, United States
Marsel Mesulam, Northwestern University Feinberg School of Medicine, Chicago, United States
Changiz Geula, Northwestern University Feinberg School of Medicine, Chicago, United States
Tamar Gefen, Northwestern University Feinberg School of Medicine, Chicago, United States
Category: Neurodegenerative Disorders
Keyword 1: dementia - other cortical
Keyword 2: aging disorders
Objective:
Behavioral variant frontotemporal dementia (bvFTD) is an early-onset clinical dementia syndrome characterized by progressive worsening of behavior and personality at initial stages, with peak areas of focal atrophy typically isolated to bilateral frontotemporal brain regions. Various underlying pathologies can be present, including the 4R tauopathies of Corticobasal Degeneration (CBD) or Progressive Supranuclear Palsy (PSP) pathological subtypes. This study investigated clinicopathologic concordance between bvFTD and cortical distributions of 4R-FTLD neuronal and glial markers of pathology.
Participants and Methods:
Right-handed cases with antemortem diagnoses of bvFTD and autopsy-confirmed PSP (N=5) or CBD (N=4) as the sole pathologic diagnosis were identified from the Northwestern University Alzheimer’s Disease Research Center brain bank. Paraffin-embedded sections were stained immunohistochemically with AT8 to visualize neuronal inclusions, tufted astrocytes, and coiled bodies in PSP, and neuronal inclusions, astrocytic plaques, and coiled bodies in CBD. Modified stereological analysis (MicroBrightField, MBF Bioscience) was performed on 3 regions bilaterally [middle frontal gyrus (MFG), inferior parietal lobule (IPL), and superior temporal gyrus (STG)]. One-way nonparametric ANOVAs and students’ t-tests were used to compare regional distributions of pathology.
Results:
In both PSP and CBD pathological subgroups, there was relatively symmetric predominance of cortical pathology, with highest burden in MFG (compared to STG and IPL, ~2-fold on average). Cases with CBD pathology had significantly more neuronal inclusions than cases with PSP pathology in all regions (p<0.05), whereas cases with PSP pathology displayed more glial pathology—particularly coiled bodies—compared to CBD (p<0.05).
Conclusions:
Preliminary findings of middle-frontal, and relatively symmetric, predominance of pathology in FTLD-PSP and FTLD-CBD are concordant with the bvFTD clinical phenotype. In bvFTD, CBD pathologic burden appears to be primarily neuronal, while in cases with PSP pathology it is characterized by considerably higher glial tau in cortex, offering insights into the selective vulnerability of distinct cell populations within 4R-tauopathies.
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