INS NYC 2024 Program

Poster	Poster Session 06 Program Schedule 02/15/2024 04:00 pm - 05:15 pm Room: Shubert Complex (Posters 1-60) Poster Session 06: Aging \| MCI \| Neurodegenerative Disease - PART 2 Final Abstract #53 CSF Beta-Amyloid-42 and Beta-Amyloid-40 Have Differential Associations with Temporal Plaque Burden and its Indirect Effects on Verbal Memory Performance Erica Howard, The Ohio State University, Columbus, United States Jena Moody, The Ohio State University, Columbus, United States Ann Lee, The Ohio State University, Columbus, United States Savana Jurgens, The Ohio State University, Columbus, United States Jasmeet Hayes, The Ohio State University, Columbus, United States Category: Dementia (Alzheimer's Disease) Keyword 1: dementia - Alzheimer's disease Keyword 2: positron emission tomography Keyword 3: temporal lobes Objective: Alzheimer’s disease (AD) is associated with the accumulation of beta-amyloid (Ab) plaques, which may be caused by Ab overproduction and dysregulation. Studies have shown that increased cerebrospinal fluid (CSF) levels of Ab peptides may be indicative of this Ab dysregulation years before pathological Ab plaques begin to aggregate. Shorter Ab-40 species are more soluble and abundant in CSF, whereas the hydrophobic and fibrillogenic Ab-42 peptide has higher aggregational propensity. As Ab sequestration onto plaques increases, CSF Ab levels typically decrease. Taken together, these findings suggest that early CSF Ab-40 increases may be important indicators of Ab dysregulation, whereas CSF Ab-42 changes may be more reflective of global plaque development. Here, we aimed to explore the relationship between these CSF peptides and in vivo Ab plaque burden and relate these changes to AD-related cognitive change in an AD-vulnerable population. Participants and Methods: We selected 110 non-demented Veterans (Age: M=68.1; 47.3% traumatic brain injury [TBI] history) from the Alzheimer’s Disease Neuroimaging Initiative-Department of Defense database based on available cognitive, CSF (Ab-40, Ab-42), and florbetapir (AV45) positron emission tomography (PET) data. The Rey Auditory Verbal Learning Test (RAVLT) and Boston Naming Test (BNT) assessed verbal memory and confrontation naming performance, respectively. Percent-retention (PCT_RET) scores were calculated for RAVLT by dividing the number of words recalled at delay by the maximum number of words recalled on learning trials. CSF Ab concentrations were measured using mass spectrometry. PET scans were processed to obtain weighted standardized uptake value ratios (SUVRs) in four Freesurfer-defined regions (frontal, parietal, temporal, cingulate). Spearman’s correlations related regional SUVRs to cognition and CSF Ab levels. Mediation models explored the relationship between CSF Ab and cognition with regional SUVRs as mediators, using the PROCESS macro with bootstrapping and standardization. Results: CSF Ab-40 was positively associated with parietal (rho=0.19, p=0.044) and temporal (rho=0.25, p=0.009) SUVRs but not frontal or cingulate regions (p>0.05). By contrast, CSF Ab-42 was negatively associated with frontal SUVR (rho=-0.21, p=0.030) but not cingulate, parietal, or temporal areas (p>0.05). After removing influential points and adjusting for age and TBI, only the associations between regional SUVRs and CSF Ab-40 remained significant. Both parietal and temporal SUVRs were negatively associated with PCT_RET (parietal: rho=-0.25, p=0.008; temporal: rho=-0.27) but not BNT scores (p>0.1). These results informed a mediation model, which revealed an indirect effect of temporal SUVR on the relationship between CSF Ab-40 and PCT-RET scores (b= -0.07, Bootstrapped 95% CI [-0.163, -0.004]), adjusting for age and TBI. Increased CSF Ab-40 was associated with increased temporal SUVR (b< 0.001, p=0.005), and high temporal SUVR, in turn, was associated with lower PCT-RET scores (b= -0.26, p=0.011). The mediation model with parietal SUVR was not significant. Conclusions: Results highlight the differential association between in vivo plaque burden and Ab-40 and Ab-42. Increased CSF Ab-40 may be indicative of an early, preclinical stage of Ab dysregulation implicating the temporal lobe whereas reduced CSF Ab-42 may be more relevant at later stages of Ab accumulation. Verbal memory retention performance may be a valuable cognitive marker of these early Ab changes.

Poster

02/15/2024
04:00 pm - 05:15 pm
Room: Shubert Complex (Posters 1-60)

Poster Session 06: Aging | MCI | Neurodegenerative Disease - PART 2

Final Abstract #53

CSF Beta-Amyloid-42 and Beta-Amyloid-40 Have Differential Associations with Temporal Plaque Burden and its Indirect Effects on Verbal Memory Performance

Erica Howard, The Ohio State University, Columbus, United States
Jena Moody, The Ohio State University, Columbus, United States
Ann Lee, The Ohio State University, Columbus, United States
Savana Jurgens, The Ohio State University, Columbus, United States
Jasmeet Hayes, The Ohio State University, Columbus, United States

Category: Dementia (Alzheimer's Disease)

Keyword 1: dementia - Alzheimer's disease
Keyword 2: positron emission tomography
Keyword 3: temporal lobes

Objective:

Alzheimer’s disease (AD) is associated with the accumulation of beta-amyloid (Ab) plaques, which may be caused by Ab overproduction and dysregulation. Studies have shown that increased cerebrospinal fluid (CSF) levels of Ab peptides may be indicative of this Ab dysregulation years before pathological Ab plaques begin to aggregate. Shorter Ab-40 species are more soluble and abundant in CSF, whereas the hydrophobic and fibrillogenic Ab-42 peptide has higher aggregational propensity. As Ab sequestration onto plaques increases, CSF Ab levels typically decrease. Taken together, these findings suggest that early CSF Ab-40 increases may be important indicators of Ab dysregulation, whereas CSF Ab-42 changes may be more reflective of global plaque development. Here, we aimed to explore the relationship between these CSF peptides and in vivo Ab plaque burden and relate these changes to AD-related cognitive change in an AD-vulnerable population.

Participants and Methods:

We selected 110 non-demented Veterans (Age: M=68.1; 47.3% traumatic brain injury [TBI] history) from the Alzheimer’s Disease Neuroimaging Initiative-Department of Defense database based on available cognitive, CSF (Ab-40, Ab-42), and florbetapir (AV45) positron emission tomography (PET) data. The Rey Auditory Verbal Learning Test (RAVLT) and Boston Naming Test (BNT) assessed verbal memory and confrontation naming performance, respectively. Percent-retention (PCT_RET) scores were calculated for RAVLT by dividing the number of words recalled at delay by the maximum number of words recalled on learning trials. CSF Ab concentrations were measured using mass spectrometry. PET scans were processed to obtain weighted standardized uptake value ratios (SUVRs) in four Freesurfer-defined regions (frontal, parietal, temporal, cingulate). Spearman’s correlations related regional SUVRs to cognition and CSF Ab levels. Mediation models explored the relationship between CSF Ab and cognition with regional SUVRs as mediators, using the PROCESS macro with bootstrapping and standardization.

Results:

CSF Ab-40 was positively associated with parietal (rho=0.19, p=0.044) and temporal (rho=0.25, p=0.009) SUVRs but not frontal or cingulate regions (p>0.05). By contrast, CSF Ab-42 was negatively associated with frontal SUVR (rho=-0.21, p=0.030) but not cingulate, parietal, or temporal areas (p>0.05). After removing influential points and adjusting for age and TBI, only the associations between regional SUVRs and CSF Ab-40 remained significant. Both parietal and temporal SUVRs were negatively associated with PCT_RET (parietal: rho=-0.25, p=0.008; temporal: rho=-0.27) but not BNT scores (p>0.1). These results informed a mediation model, which revealed an indirect effect of temporal SUVR on the relationship between CSF Ab-40 and PCT-RET scores (b= -0.07, Bootstrapped 95% CI [-0.163, -0.004]), adjusting for age and TBI. Increased CSF Ab-40 was associated with increased temporal SUVR (b< 0.001, p=0.005), and high temporal SUVR, in turn, was associated with lower PCT-RET scores (b= -0.26, p=0.011). The mediation model with parietal SUVR was not significant.

Conclusions:

Results highlight the differential association between in vivo plaque burden and Ab-40 and Ab-42. Increased CSF Ab-40 may be indicative of an early, preclinical stage of Ab dysregulation implicating the temporal lobe whereas reduced CSF Ab-42 may be more relevant at later stages of Ab accumulation. Verbal memory retention performance may be a valuable cognitive marker of these early Ab changes.