Elevated plasma p-tau231 is associated with reduced generalization and medial temporal lobe dynamic network
Miray Budak1, Bernadette A Fausto2, Zuzanna Osiecka2
1Center for Molecular & Behavioral Neuroscience, Rutgers University-Newark, 197 University Avenue, Suite 209, Newark, NJ, 07102, USA. miray.budak@rutgers.edu.
Background:
Phosphorylated tau (p-tau) and amyloid beta (Aβ) in human plasma may provide an affordable and minimally invasive method to evaluate Alzheimer's disease (AD) pathophysiology. The medial temporal lobe (MTL) is susceptible to changes in structural integrity that are indicative of the disease progression. Among healthy adults, higher dynamic network flexibility within the MTL was shown to mediate better generalization of prior learning, a measure which has been demonstrated to predict cognitive decline and neural changes in preclinical AD longitudinally. Recent developments in cognitive, neural, and blood-based biomarkers of AD risk that may correspond with MTL changes. However, there is no comprehensive study on how these generalization biomarkers, long-term memory, MTL dynamic network flexibility, and plasma biomarkers are interrelated. This study investigated (1) the relationship between long-term memory, generalization performance, and MTL dynamic network flexibility and (2) how plasma p-tau231, p-tau181, and Aβ42/Aβ40 influence generalization, long-term memory, and MTL dynamics in cognitively unimpaired older African Americans.
Methods:
148 participants (Meanage: 70.88,SDage: 6.05) were drawn from the ongoing longitudinal study, Pathways to Healthy Aging in African Americans conducted at Rutgers University-Newark. Cognition was evaluated with the Rutgers Acquired Equivalence Task (generalization task) and Rey Auditory Learning Test (RAVLT) delayed recall. MTL dynamic network connectivity was measured from functional Magnetic Resonance Imaging data. Plasma p-tau231, p-tau181, and Aβ42/Aβ40 were measured from blood samples.
Results:
There was a significant positive correlation between generalization performance and MTL Dynamic Network Flexibility (t = 3.372, β = 0.280, p < 0.001). There were significant negative correlations between generalization performance and plasma p-tau231 (t = -3.324, β = -0.265, p = 0.001) and p-tau181 (t = -2.408, β = -0.192, p = 0.017). A significant negative correlation was found between plasma p-tau231 and MTL Dynamic Network Flexibility (t = -2.825, β = -0.232, p = 0.005).
Conclusions:
Increased levels of p-tau231 are associated with impaired generalization abilities and reduced dynamic network flexibility within the MTL. Plasma p-tau231 may serve as a potential biomarker for assessing cognitive decline and neural changes in cognitively unimpaired older African Americans.
Insights
Higher plasma phosphorylated tau (p-tau) levels, specifically p-tau231, are linked to impaired generalization abilities and reduced medial temporal lobe (MTL) network flexibility in older African Americans, suggesting p-tau231 as a potential biomarker for cognitive decline.
Area of Science:
- Neuroscience
- Biomarkers
- Cognitive Aging
Background:
- Plasma phosphorylated tau (p-tau) and amyloid beta (Aβ) offer minimally invasive Alzheimer's disease (AD) assessment.
- Medial temporal lobe (MTL) integrity changes indicate AD progression.
- MTL dynamic network flexibility predicts cognitive decline and neural changes in preclinical AD.
Purpose of the Study:
- Investigate relationships between long-term memory, generalization, and MTL dynamic network flexibility.
- Determine how plasma p-tau231, p-tau181, and Aβ42/Aβ40 influence generalization, memory, and MTL dynamics.
- Examine these factors in cognitively unimpaired older African Americans.
Main Methods:
- 148 cognitively unimpaired older African Americans participated.
- Generalization assessed via Rutgers Acquired Equivalence Task; long-term memory via RAVLT delayed recall.
- MTL dynamic network connectivity measured using fMRI; plasma biomarkers (p-tau231, p-tau181, Aβ42/Aβ40) quantified.
Main Results:
- Generalization performance positively correlated with MTL Dynamic Network Flexibility.
- Generalization performance negatively correlated with plasma p-tau231 and p-tau181.
- Plasma p-tau231 negatively correlated with MTL Dynamic Network Flexibility.
Conclusions:
- Elevated plasma p-tau231 associated with impaired generalization and reduced MTL dynamic network flexibility.
- Plasma p-tau231 may indicate cognitive decline and neural changes in unimpaired older African Americans.
- These findings highlight p-tau231 as a potential blood-based biomarker for early AD-related changes.
