The nucleus basalis of Meynert influences tau accumulation through global brain activity
Poster No:
229
Submission Type:
Abstract Submission
Authors:
Yutong Mao1, Baizhou Pan1, Xiao Liu1,2
Institutions:
1Department of Biomedical Engineering, The Pennsylvania State University, State College, PA, 2Institute for Computational and Data Sciences, The Pennsylvania State University,, State College, PA
First Author:
Yutong Mao
Department of Biomedical Engineering, The Pennsylvania State University
State College, PA
Department of Biomedical Engineering, The Pennsylvania State University
State College, PA
Co-Author(s):
Baizhou Pan
Department of Biomedical Engineering, The Pennsylvania State University
State College, PA
Department of Biomedical Engineering, The Pennsylvania State University
State College, PA
Xiao Liu
Department of Biomedical Engineering, The Pennsylvania State University|Institute for Computational and Data Sciences, The Pennsylvania State University,
State College, PA|State College, PA
Department of Biomedical Engineering, The Pennsylvania State University|Institute for Computational and Data Sciences, The Pennsylvania State University,
State College, PA|State College, PA
Introduction:
The nucleus basalis of Meynert (NbM), a key cholinergic structure in the basal forebrain, plays a critical role in Alzheimer's disease (AD) (Fernández-Cabello et al., 2020; Schmitz & Nathan Spreng, 2016). Its degeneration correlates with cognitive decline and pathological progression, such as tau accumulation (Lo et al., 2020), in AD. Meanwhile, recent studies have identified a highly structured infra-slow (<0.1 Hz) global brain activity (Gu et al., 2021; Liu et al., 2021) and demonstrated its relevance to AD pathology, including amyloid-β (Aβ) and tau accumulations (Han et al., 2021, 2023). Interestingly, the NbM appeared to regulate this global activity (Gu et al., 2021; Liu et al., 2018; Turchi et al., 2018), which may thus mediate the association between NbM degeneration and tau accumulation. Using multimodal, longitudinal data from the Alzheimer's Disease Neuroimage Initiative (ADNI), we tested this hypothesis by examining the relationship between the NbM degeneration, global brain activity, and tau accumulation at the preclinical and prodromal stages of AD.
Methods:
We selected 40 cognitively normal (CN) and significant memory concern (SMC) participants and 35 mild cognitive impairment (MCI) patients from ADNI3. The CN/SMC participants were further classified into abnormal (pTau/Aβ ≥ 0.028; aCSF) and normal (pTau/Aβ < 0.028, nCSF) CSF groups (Fernández-Cabello et al., 2020). The NbM volume was computed on structural MRI based on the Ch4 region of a stereotaxic probabilistic map and adjusted for total intracranial volume, age, and sex (Schmitz & Nathan Spreng, 2016). Tau-PET regional standardized uptake value ratios (SUVRs) data were directly obtained from the ADNI. The global brain activity was quantified by global co-activation pattern (gCAP) at big peaks of global mean fMRI BOLD (gBOLD) signal (Liu et al., 2018). We examined the correlations among these metrics across different patient groups and for four ROI sets defined according to Braak staging (Schöll et al., 2016).
Results:
Smaller NbM volumes are associated with higher cortical tau SUVR (ρ = -0.48, p = 1.16×10-5) across all selected subjects (Fig. 1B). This relationship is significant for both CN/SMC aCSF (ρ = -0.51, p = 0.03, Fig. 1E) and MCI (ρ = -0.54, p = 0.001, Fig. 1G) groups but absent in the CN/SMC nCSF group (ρ = 0.13, p = 0.54, Fig. 1C). Furthermore, baseline NbM volumes predict tau changes in follow-up experiments (time interval: 614 ± 337 days) for both groups (CN/SMC aCSF: ρ = -0.53, p = 0.03, Fig. 1F; MCI: ρ = -0.42, p = 0.01, Fig. 1H), but not for the CN/SMC nCSF group (ρ = 0.01, p = 0.96, Fig. 1D). In comparison, the baseline tau level only marginally predicts NbM volume changes in the CN/SMC aCSF group (ρ = -0.46, p = 0.06, Fig. 1F).
The global brain activity, as quantified by gCAP, correlates with NbM volume and tau in a spatially corresponding manner. In the CN/SMC aCSF group, smaller NbM volumes are associated with weaker gCAP activations in cortical regions known for early tau accumulation, including the entorhinal cortex. Importantly, weaker gCAP activations are indeed associated with higher regional tau SUVR in similar brain regions, resulting in comparable patterns of gCAP-NbM and gCAP-tau correlational maps (ρ = -0.55, p = 1.15 × 10-6, Fig. 2B). Moreover, the gCAP-tau correlation is most significantly in the Braak I region and gradually diminished across ROI sets progressively associated with AD pathology (Fig. 2C). Similar results were observed in the MCI group (Fig. 2D-2E). But the gCAP-tau associations extend to much broader brain regions, with significant correlations observed in the Braak III–IV and V-VI ROI sets.
The global brain activity, as quantified by gCAP, correlates with NbM volume and tau in a spatially corresponding manner. In the CN/SMC aCSF group, smaller NbM volumes are associated with weaker gCAP activations in cortical regions known for early tau accumulation, including the entorhinal cortex. Importantly, weaker gCAP activations are indeed associated with higher regional tau SUVR in similar brain regions, resulting in comparable patterns of gCAP-NbM and gCAP-tau correlational maps (ρ = -0.55, p = 1.15 × 10-6, Fig. 2B). Moreover, the gCAP-tau correlation is most significantly in the Braak I region and gradually diminished across ROI sets progressively associated with AD pathology (Fig. 2C). Similar results were observed in the MCI group (Fig. 2D-2E). But the gCAP-tau associations extend to much broader brain regions, with significant correlations observed in the Braak III–IV and V-VI ROI sets.
· Association s between NbM volume, tau SUVR, and tau progression in different participant groups
·Spatial associations between global co-activation patterns (gCAP), tau SUVR, and NbM volume across participant groups
Conclusions:
The findings suggest a link between NbM degeneration and tau accumulation in the preclinical and prodromal stages of AD. Notably, this relationship appeared to be mediated by infra-slow global brain activity.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
Task-Independent and Resting-State Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Subcortical Structures
Novel Imaging Acquisition Methods:
Anatomical MRI
BOLD fMRI 2
Keywords:
FUNCTIONAL MRI
STRUCTURAL MRI
Other - The nucleus basalis of Meynert, tau, global brain activity
1|2Indicates the priority used for review
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Provide references using APA citation style.
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