INS NYC 2024 Program

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 #62 Disease-Specific Severity of Amygdalar Inflammation in 3R vs 4R FTLD-tauopathies Rachel Keszycki, Northwestern University, Chicago, United States Allegra Kawles, Northwestern University, Chicago, United States Grace Minogue, Northwestern University, Chicago, United States Antonia Zouridakis, Northwestern University, Chicago, United States Alyssa Macomber, Northwestern University, Chicago, United States Vivienne Lubbat, Northwestern University, Chicago, United States Sandra Weintraub, Northwestern University, Chicago, United States Nathan Gill, Northwestern University, Chicago, United States Rudolph Castellani, Northwestern University, Chicago, United States M-Marsel Mesulam, Northwestern University, Chicago, United States Changiz Geula, Northwestern University, Chicago, United States Tamar Gefen, Northwestern University, Chicago, United States Category: Neurodegenerative Disorders Keyword 1: dementia - other cortical Objective: Primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD) are dementia syndromes characterized by primary language impairment and changes in personality and comportment, respectively. Frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau) is a neurodegenerative disease that can underly both syndromes. There are several subtypes of FTLD-tau characterized by distinct pathologic inclusion morphology and areas of peak atrophy, including Pick’s disease (PiD), a 3R tauopathy, and corticobasal degeneration (CBD), a 4R tauopathy. Prior research suggests that limbic regions such as the amygdala may be differentially affected across neurodegenerative diseases and may be implicated in distinct neuropsychiatric presentations in dementia. This study examined activated microglia as a marker of inflammation in the amygdala of individuals with antemortem diagnosis of PPA or bvFTD and postmortem PiD or CBD neuropathology. The goal was to determine whether amygdalar pathology contributes to clinical symptoms unique to dementias due to 3R vs 4R FTLD-tau. Participants and Methods: Right-handed participants with autopsy-confirmed PiD or CBD and antemortem clinical diagnoses of PPA (PiD N=8, CBD N=10) or bvFTD (PiD N=9, CBD N=6) were identified from the Northwestern Alzheimer’s Disease Research Center brain bank. Unilateral amygdala sections (25 left, 8 right) were immunostained using an antibody against HLA-DR to visualize activated microglia, a marker of neuroinflammation. We quantified the percent area of HLA-DR immunopositivity and number of activated microglia per mm² via HALO software (Indica Labs) and conducted a two-way ANOVA with clinical and pathologic groups as dependent variables. We also performed Welch’s t-tests to compare PiD and CBD within each clinical diagnostic group. Results: Across all cases, those with PiD showed a significantly greater percent area of HLA-DR immunopositivity than those with CBD (3.69% vs. 0.71%, p<0.01). Average number of activated microglia per mm² was also greater in those with PiD than in those with CBD (23.28 vs. 105.40, p<0.01). This finding appeared to be primarily driven by cases with bvFTD; compared to bvFTD-PiD, bvFTD-CBD showed significantly lower HLA-DR immunopositivity (4.91% vs. 0.35%, p<0.05) and number of activated microglia (143.60 vs. 10.78, p<0.05). In PPA cases, HLA-DR immunopositivity and activated microglia per mm² also tended to be higher in PiD than in CBD, although the difference did not reach significance. Conclusions: Our findings indicate that neuroinflammation in the amygdala is more severe in PiD than in CBD, and this difference is more pronounced in bvFTD than in PPA. This suggests that microglial activation in the amygdala may play a particularly salient role in personality and comportmental disruption in patients with an underlying 3R-FTLD tauopathy. Future studies will investigate the relationship of neuroinflammation and pathologic inclusions in the amygdala to behavioral and psychiatric symptoms across the entirety of the FTLD spectrum.

Poster

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 #62

Disease-Specific Severity of Amygdalar Inflammation in 3R vs 4R FTLD-tauopathies

Rachel Keszycki, Northwestern University, Chicago, United States
Allegra Kawles, Northwestern University, Chicago, United States
Grace Minogue, Northwestern University, Chicago, United States
Antonia Zouridakis, Northwestern University, Chicago, United States
Alyssa Macomber, Northwestern University, Chicago, United States
Vivienne Lubbat, Northwestern University, Chicago, United States
Sandra Weintraub, Northwestern University, Chicago, United States
Nathan Gill, Northwestern University, Chicago, United States
Rudolph Castellani, Northwestern University, Chicago, United States
M-Marsel Mesulam, Northwestern University, Chicago, United States
Changiz Geula, Northwestern University, Chicago, United States
Tamar Gefen, Northwestern University, Chicago, United States

Category: Neurodegenerative Disorders

Keyword 1: dementia - other cortical

Objective:

Primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD) are dementia syndromes characterized by primary language impairment and changes in personality and comportment, respectively. Frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau) is a neurodegenerative disease that can underly both syndromes. There are several subtypes of FTLD-tau characterized by distinct pathologic inclusion morphology and areas of peak atrophy, including Pick’s disease (PiD), a 3R tauopathy, and corticobasal degeneration (CBD), a 4R tauopathy. Prior research suggests that limbic regions such as the amygdala may be differentially affected across neurodegenerative diseases and may be implicated in distinct neuropsychiatric presentations in dementia. This study examined activated microglia as a marker of inflammation in the amygdala of individuals with antemortem diagnosis of PPA or bvFTD and postmortem PiD or CBD neuropathology. The goal was to determine whether amygdalar pathology contributes to clinical symptoms unique to dementias due to 3R vs 4R FTLD-tau.

Participants and Methods:

Right-handed participants with autopsy-confirmed PiD or CBD and antemortem clinical diagnoses of PPA (PiD N=8, CBD N=10) or bvFTD (PiD N=9, CBD N=6) were identified from the Northwestern Alzheimer’s Disease Research Center brain bank. Unilateral amygdala sections (25 left, 8 right) were immunostained using an antibody against HLA-DR to visualize activated microglia, a marker of neuroinflammation. We quantified the percent area of HLA-DR immunopositivity and number of activated microglia per mm² via HALO software (Indica Labs) and conducted a two-way ANOVA with clinical and pathologic groups as dependent variables. We also performed Welch’s t-tests to compare PiD and CBD within each clinical diagnostic group.

Results:

Across all cases, those with PiD showed a significantly greater percent area of HLA-DR immunopositivity than those with CBD (3.69% vs. 0.71%, p<0.01). Average number of activated microglia per mm² was also greater in those with PiD than in those with CBD (23.28 vs. 105.40, p<0.01). This finding appeared to be primarily driven by cases with bvFTD; compared to bvFTD-PiD, bvFTD-CBD showed significantly lower HLA-DR immunopositivity (4.91% vs. 0.35%, p<0.05) and number of activated microglia (143.60 vs. 10.78, p<0.05). In PPA cases, HLA-DR immunopositivity and activated microglia per mm² also tended to be higher in PiD than in CBD, although the difference did not reach significance.

Conclusions:

Our findings indicate that neuroinflammation in the amygdala is more severe in PiD than in CBD, and this difference is more pronounced in bvFTD than in PPA. This suggests that microglial activation in the amygdala may play a particularly salient role in personality and comportmental disruption in patients with an underlying 3R-FTLD tauopathy. Future studies will investigate the relationship of neuroinflammation and pathologic inclusions in the amygdala to behavioral and psychiatric symptoms across the entirety of the FTLD spectrum.