INS NYC 2024 Program

Poster	Poster Session 02 Program Schedule 02/15/2024 08:00 am - 09:15 am Room: Shubert Complex (Posters 1-60) Poster Session 02: Aging \| MCI \| Neurodegenerative Disease - PART 1 Final Abstract #45 Stathmin-2 (STMN2) as a Potential Substrate of Cytoskeletal Integrity in Cognitive SuperAgers Allegra Kawles, Northwestern University, Chicago, United States Christopher Mazurek, Northwestern University, Chicago, United States Antonia Zouridakis, Northwestern University, Chicago, United States Grace Minogue, Northwestern University, Chicago, United States Alyssa Macomber, Northwestern University, Chicago, United States Rachel Keszycki, Northwestern University, Chicago, United States Sarat Vatsavayai, University of California San Francisco, San Francisco, United States Benayahu Elbaz-Eilon, Northwestern University, Chicago, United States Rudolph Castellani, Northwestern University, Chicago, United States M Mesulam, Northwestern University, Chicago, United States William Seeley, University of California San Francisco, San Francisco, United States Emily Rogalski, University of Chicago, Chicago, United States Changiz Geula, Northwestern University, Chicago, United States Tamar Gefen, Northwestern University, Chicago, United States Category: Aging Keyword 1: aging (normal) Keyword 2: hippocampus Keyword 3: memory: normal Objective: SuperAgers are individuals aged 80 or older with memory performance similar to those 20-30 years their junior. Previous studies have found several unique neurobiological features of SuperAgers compared to their cognitively average same-aged peers (Normal Old), including less Alzheimer’s pathology and larger, healthier neurons in the entorhinal cortex (ERC), a core memory-related limbic region. Stathmin-2 (STMN2) is a microtubule-associated protein expressed in neurons and required for cytoskeletal stabilization and axon outgrowth and maintenance. Decreased STMN2 expression has been linked to the presence of several age-related neurodegenerative diseases, including Alzheimer’s disease. Increased STMN2 expression is thought to play a protective role in neuronal health, while excessive expression has been shown to have detrimental effects on neuronal health. Our objective was to explore whether STMN2 expression in the entorhinal cortex is a potential substrate of neuronal integrity across the successful cognitive aging spectrum. Participants and Methods: Specimens from SuperAgers and Normal Old (N=4 per group) were acquired from the Northwestern University Alzheimer’s Disease Research Center (ADRC) Brain Bank and the SuperAging Research Program. Paraffin-embedded anterior hippocampal sections that included the ERC were immunohistochemically stained with STMN2 antibody to visualize STMN2 expression. A digital image of each slide was obtained at 20X magnification using the Olympus VS200 Slide Scanner for analysis. Using QuPath software (v.0.4.3), the ERC was traced as a guide at 0.5x magnification. A 500 µm x 500µm grid was superimposed on the image, and perikarya of ~2 STMN2-positive neurons per grid square were traced. Traced neurons were analyzed for optical density (OD) due to STMN2 immunopositivity. Unpaired t-tests were used to compare age at death and Braak stage (a measure of neurofibrillary tangle burden) between groups. A nonparametric Mann-Whitney t-test was utilized to compare STMN2 OD between groups, and a Spearman correlation was used to analyze the relationship between STMN2 OD and age at death. Results: There was no significant difference in age at death (range, 82-101) or Braak stage between groups. Normal Old showed significantly higher average STMN2 OD per neuron in the ERC (M=0.136, SD=0.075) compared to SuperAgers (M=0.078, SD=0.041) (p<0.001). There was a positive correlation between age and STMN2 OD across all participants that trended towards significance (r=0.57, p=0.076). Conclusions: Preliminary findings indicate that SuperAgers may express less STMN2 than Normal Old in ERC neurons, despite comparable Braak stage, reflecting a possible substrate for superior memory. Lower STMN2 expression in SuperAgers may be due to healthier neuronal cytoskeleton in these individuals, obviating the need for increased STMN2. The positive relationship between age at death and STMN2 suggests that preserved cognition in the oldest-old may be supported by STMN2-mediated cytoprotection in pyramidal neurons. Future studies are needed to corroborate findings by examining additional limbic and neocortical regions in a larger cohort of successful agers and those with memory impairment due to Alzheimer’s disease.

Poster

02/15/2024
08:00 am - 09:15 am
Room: Shubert Complex (Posters 1-60)

Poster Session 02: Aging | MCI | Neurodegenerative Disease - PART 1

Final Abstract #45

Stathmin-2 (STMN2) as a Potential Substrate of Cytoskeletal Integrity in Cognitive SuperAgers

Allegra Kawles, Northwestern University, Chicago, United States
Christopher Mazurek, Northwestern University, Chicago, United States
Antonia Zouridakis, Northwestern University, Chicago, United States
Grace Minogue, Northwestern University, Chicago, United States
Alyssa Macomber, Northwestern University, Chicago, United States
Rachel Keszycki, Northwestern University, Chicago, United States
Sarat Vatsavayai, University of California San Francisco, San Francisco, United States
Benayahu Elbaz-Eilon, Northwestern University, Chicago, United States
Rudolph Castellani, Northwestern University, Chicago, United States
M Mesulam, Northwestern University, Chicago, United States
William Seeley, University of California San Francisco, San Francisco, United States
Emily Rogalski, University of Chicago, Chicago, United States
Changiz Geula, Northwestern University, Chicago, United States
Tamar Gefen, Northwestern University, Chicago, United States

Category: Aging

Keyword 1: aging (normal)
Keyword 2: hippocampus
Keyword 3: memory: normal

Objective:

SuperAgers are individuals aged 80 or older with memory performance similar to those 20-30 years their junior. Previous studies have found several unique neurobiological features of SuperAgers compared to their cognitively average same-aged peers (Normal Old), including less Alzheimer’s pathology and larger, healthier neurons in the entorhinal cortex (ERC), a core memory-related limbic region. Stathmin-2 (STMN2) is a microtubule-associated protein expressed in neurons and required for cytoskeletal stabilization and axon outgrowth and maintenance. Decreased STMN2 expression has been linked to the presence of several age-related neurodegenerative diseases, including Alzheimer’s disease. Increased STMN2 expression is thought to play a protective role in neuronal health, while excessive expression has been shown to have detrimental effects on neuronal health. Our objective was to explore whether STMN2 expression in the entorhinal cortex is a potential substrate of neuronal integrity across the successful cognitive aging spectrum.

Participants and Methods:

Specimens from SuperAgers and Normal Old (N=4 per group) were acquired from the Northwestern University Alzheimer’s Disease Research Center (ADRC) Brain Bank and the SuperAging Research Program. Paraffin-embedded anterior hippocampal sections that included the ERC were immunohistochemically stained with STMN2 antibody to visualize STMN2 expression. A digital image of each slide was obtained at 20X magnification using the Olympus VS200 Slide Scanner for analysis. Using QuPath software (v.0.4.3), the ERC was traced as a guide at 0.5x magnification. A 500 µm x 500µm grid was superimposed on the image, and perikarya of ~2 STMN2-positive neurons per grid square were traced. Traced neurons were analyzed for optical density (OD) due to STMN2 immunopositivity. Unpaired t-tests were used to compare age at death and Braak stage (a measure of neurofibrillary tangle burden) between groups. A nonparametric Mann-Whitney t-test was utilized to compare STMN2 OD between groups, and a Spearman correlation was used to analyze the relationship between STMN2 OD and age at death.

Results:

There was no significant difference in age at death (range, 82-101) or Braak stage between groups. Normal Old showed significantly higher average STMN2 OD per neuron in the ERC (M=0.136, SD=0.075) compared to SuperAgers (M=0.078, SD=0.041) (p<0.001). There was a positive correlation between age and STMN2 OD across all participants that trended towards significance (r=0.57, p=0.076).

Conclusions:

Preliminary findings indicate that SuperAgers may express less STMN2 than Normal Old in ERC neurons, despite comparable Braak stage, reflecting a possible substrate for superior memory. Lower STMN2 expression in SuperAgers may be due to healthier neuronal cytoskeleton in these individuals, obviating the need for increased STMN2. The positive relationship between age at death and STMN2 suggests that preserved cognition in the oldest-old may be supported by STMN2-mediated cytoprotection in pyramidal neurons. Future studies are needed to corroborate findings by examining additional limbic and neocortical regions in a larger cohort of successful agers and those with memory impairment due to Alzheimer’s disease.