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 #32 Sex differences in the Association Between Neuroinflammatory Markers and Cognitive Performance in Autosomal Dominant Alzheimer’s Disease Taryn Gordon, George Fox University, Newberg, United States Clara Vila-Castelar, Massachusetts General Hospital, Harvard Medical School, Boston, United States Stephanie Langella, Massachusetts General Hospital, Harvard Medical School, Boston, United States Diana Munera, Massachusetts General Hospital, Harvard Medical School, Boston, United States Ana Baena, Grupo de Neurociencias de Antioquia, Facultad de Medicina, Universidad de Antioquia, Mendellin, Colombia Jairo Martinez, Massachusetts General Hospital, Harvard Medical School, Boston, United States Averi Giudicessi, Massachusetts General Hospital, Harvard Medical School, Boston, United States Edmarie Guzman-Velez, Massachusetts General Hospital, Harvard Medical School, Boston, United States Francisco Lopera, Grupo de Neurociencias de Antioquia, Facultad de Medicina, Universidad de Antioquia, Medellin, Colombia Yakeel Quiroz, Massachusetts General Hospital, Harvard Medical School, Boston, United States Category: Dementia (Alzheimer's Disease) Keyword 1: dementia - Alzheimer's disease Keyword 2: neurophysiology Keyword 3: neurocognition Objective: Neuroinflammation is a prominent feature of Alzheimer’s disease (AD) pathophysiology. Glial Fibrillary Acidic Protein (GFAP), a marker of astrocyte reactivity, has emerged as a biomarker of neuroinflammation in AD, as levels increase with AD progression. Individuals with autosomal dominant AD (ADAD) due to the Presenilin 1 (PSEN1) E280A mutation develop early onset dementia in their forties with near certainty, and provide a unique opportunity to study preclinical changes associated with AD. A previous study of an ADAD sample showed increased plasma GFAP levels in carriers compared to non-carriers, approximately 10 years before clinical onset. To our knowledge, there is no research examining sex differences in GFAP plasma concentration in ADAD. We aimed to investigate sex differences in the potential relationship between GFAP levels and cognitive performance in PSEN1 E280A mutation carriers. Participants and Methods: A total of 100 mutation carriers (90 cognitively unimpaired: [Age: 31.41 +/- 4.99 years; 58 females], 10 mildly impaired: [Age: 43.80 +/- 2.74 years; 6 females]), and 99 age-matched non-carrier family members (Age: 36.43 +/- 6.82 years; 63 females) from the Colombia-Boston (COLBOS) biomarker study with cross-sectional plasma GFAP measures and cognitive assessments were included. Global cognition was measured with the Mini-Mental Status Examination (MMSE) and memory performance was measured with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Learning Delayed Recall (WLL). Mann-Whitney U test compared group differences between carriers and non-carriers, and males and females among carriers and non-carriers. Spearman correlations were used to determine associations among GFAP and cognitive performance in carriers and non-carriers, stratified by sex. Results: Carriers had higher levels of GFAP than non-carriers (carrier mean: 108.13 (+/- 90.72); non-carrier mean: 57.90 (+/- 31.72); p <0.001). In carriers, higher levels of GFAP were associated with lower MMSE total score (r=-0.327, p =0.002) and lower WLL scores (r=-0.480, p <0.001). GFAP was not associated with cognitive performance among non-carriers. There were no sex differences in GFAP levels among carrier or non-carrier groups (p>0.05). Across female carriers, higher levels of GFAP were associated with lower MMSE total score (r=-0.410, p <0.001) and lower WLL (r=-0.602, p <0.001), while in male carriers there was no significant association between GFAP levels and MMSE (r=-0.217, p=0.204) or WLL (r=-0.308, p=0.067). There were no sex differences in the associations between GFAP and cognitive performance among non-carriers. Conclusions: Higher levels of plasma GFAP were associated with worse global cognition and memory performance among PSEN1 E280A mutation carriers, particularly among females. These findings highlight the potential of plasma GFAP as an AD biomarker, as well as the importance of considering sex-specific effects of AD-related neuroinflammation, neurodegeneration and cognitive decline. Further longitudinal investigations with larger cohorts are warranted to validate and expand upon these findings.

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 #32

Sex differences in the Association Between Neuroinflammatory Markers and Cognitive Performance in Autosomal Dominant Alzheimer’s Disease

Taryn Gordon, George Fox University, Newberg, United States
Clara Vila-Castelar, Massachusetts General Hospital, Harvard Medical School, Boston, United States
Stephanie Langella, Massachusetts General Hospital, Harvard Medical School, Boston, United States
Diana Munera, Massachusetts General Hospital, Harvard Medical School, Boston, United States
Ana Baena, Grupo de Neurociencias de Antioquia, Facultad de Medicina, Universidad de Antioquia, Mendellin, Colombia
Jairo Martinez, Massachusetts General Hospital, Harvard Medical School, Boston, United States
Averi Giudicessi, Massachusetts General Hospital, Harvard Medical School, Boston, United States
Edmarie Guzman-Velez, Massachusetts General Hospital, Harvard Medical School, Boston, United States
Francisco Lopera, Grupo de Neurociencias de Antioquia, Facultad de Medicina, Universidad de Antioquia, Medellin, Colombia
Yakeel Quiroz, Massachusetts General Hospital, Harvard Medical School, Boston, United States

Category: Dementia (Alzheimer's Disease)

Keyword 1: dementia - Alzheimer's disease
Keyword 2: neurophysiology
Keyword 3: neurocognition

Objective:

Neuroinflammation is a prominent feature of Alzheimer’s disease (AD) pathophysiology. Glial Fibrillary Acidic Protein (GFAP), a marker of astrocyte reactivity, has emerged as a biomarker of neuroinflammation in AD, as levels increase with AD progression. Individuals with autosomal dominant AD (ADAD) due to the Presenilin 1 (PSEN1) E280A mutation develop early onset dementia in their forties with near certainty, and provide a unique opportunity to study preclinical changes associated with AD. A previous study of an ADAD sample showed increased plasma GFAP levels in carriers compared to non-carriers, approximately 10 years before clinical onset. To our knowledge, there is no research examining sex differences in GFAP plasma concentration in ADAD. We aimed to investigate sex differences in the potential relationship between GFAP levels and cognitive performance in PSEN1 E280A mutation carriers.

Participants and Methods:

A total of 100 mutation carriers (90 cognitively unimpaired: [Age: 31.41 +/- 4.99 years; 58 females], 10 mildly impaired: [Age: 43.80 +/- 2.74 years; 6 females]), and 99 age-matched non-carrier family members (Age: 36.43 +/- 6.82 years; 63 females) from the Colombia-Boston (COLBOS) biomarker study with cross-sectional plasma GFAP measures and cognitive assessments were included. Global cognition was measured with the Mini-Mental Status Examination (MMSE) and memory performance was measured with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Learning Delayed Recall (WLL). Mann-Whitney U test compared group differences between carriers and non-carriers, and males and females among carriers and non-carriers. Spearman correlations were used to determine associations among GFAP and cognitive performance in carriers and non-carriers, stratified by sex.

Results:

Carriers had higher levels of GFAP than non-carriers (carrier mean: 108.13 (+/- 90.72); non-carrier mean: 57.90 (+/- 31.72); p <0.001). In carriers, higher levels of GFAP were associated with lower MMSE total score (r=-0.327, p =0.002) and lower WLL scores (r=-0.480, p <0.001). GFAP was not associated with cognitive performance among non-carriers. There were no sex differences in GFAP levels among carrier or non-carrier groups (p>0.05). Across female carriers, higher levels of GFAP were associated with lower MMSE total score (r=-0.410, p <0.001) and lower WLL (r=-0.602, p <0.001), while in male carriers there was no significant association between GFAP levels and MMSE (r=-0.217, p=0.204) or WLL (r=-0.308, p=0.067). There were no sex differences in the associations between GFAP and cognitive performance among non-carriers.

Conclusions:

Higher levels of plasma GFAP were associated with worse global cognition and memory performance among PSEN1 E280A mutation carriers, particularly among females. These findings highlight the potential of plasma GFAP as an AD biomarker, as well as the importance of considering sex-specific effects of AD-related neuroinflammation, neurodegeneration and cognitive decline. Further longitudinal investigations with larger cohorts are warranted to validate and expand upon these findings.