| 1. |
- de Flores, Robin, et al.
(författare)
-
Medial Temporal Lobe Networks in Alzheimer's Disease : Structural and Molecular Vulnerabilities
- 2022
-
Ingår i: The Journal of Neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 42:10, s. 2131-2141
-
Tidskriftsartikel (refereegranskat)abstract
- The medial temporal lobe (MTL) is connected to the rest of the brain through two main networks: the anterior-temporal (AT) and the posterior-medial (PM) systems. Given the crucial role of the MTL and networks in the physiopathology of Alzheimer's disease (AD), the present study aimed at (1) investigating whether MTL atrophy propagates specifically within the AT and PM networks, and (2) evaluating the vulnerability of these networks to AD proteinopathies. To do that, we used neuroimaging data acquired in human male and female in three distinct cohorts: (1) resting-state functional MRI (rs-fMRI) from the aging brain cohort (ABC) to define the AT and PM networks (n = 68); (2) longitudinal structural MRI from Alzheimer's disease neuroimaging initiative (ADNI)GO/2 to highlight structural covariance patterns (n = 349); and (3) positron emission tomography (PET) data from ADNI3 to evaluate the networks' vulnerability to amyloid and tau (n = 186). Our results suggest that the atrophy of distinct MTL subregions propagates within the AT and PM networks in a dissociable manner. Brodmann area (BA)35 structurally covaried within the AT network while the parahippocampal cortex (PHC) covaried within the PM network. In addition, these networks are differentially associated with relative tau and amyloid burden, with higher tau levels in AT than in PM and higher amyloid levels in PM than in AT. Our results also suggest differences in the relative burden of tau species. The current results provide further support for the notion that two distinct MTL networks display differential alterations in the context of AD. These findings have important implications for disease spread and the cognitive manifestations of AD.SIGNIFICANCE STATEMENT The current study provides further support for the notion that two distinct medial temporal lobe (MTL) networks, i.e., anterior-temporal (AT) and the posterior-medial (PM), display differential alterations in the context of Alzheimer's disease (AD). Importantly, neurodegeneration appears to occur within these networks in a dissociable manner marked by their covariance patterns. In addition, the AT and PM networks are also differentially associated with relative tau and amyloid burden, and perhaps differences in the relative burden of tau species [e.g., neurofibriliary tangles (NFTs) vs tau in neuritic plaques]. These findings, in the context of a growing literature consistent with the present results, have important implications for disease spread and the cognitive manifestations of AD in light of the differential cognitive processes ascribed to them.
|
|
| 2. |
- Lyu, Xueying, et al.
(författare)
-
Tau-neurodegeneration mismatch reveals vulnerability and resilience to comorbidities in Alzheimer's continuum
-
Ingår i: Alzheimer's and Dementia. - 1552-5260.
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Variability in relationship of tau-based neurofibrillary tangles (T) and neurodegeneration (N) in Alzheimer's disease (AD) arises from non-specific nature of N, modulated by non-AD co-pathologies, age-related changes, and resilience factors. METHODS: We used regional T-N residual patterns to partition 184 patients within the Alzheimer's continuum into data-driven groups. These were compared with groups from 159 non-AD (amyloid “negative”) patients partitioned using cortical thickness, and groups in 98 patients with ante mortem MRI and post mortem tissue for measuring N and T, respectively. We applied the initial T-N residual model to classify 71 patients in an independent cohort into predefined groups. RESULTS: AD groups displayed spatial T-N mismatch patterns resembling neurodegeneration patterns in non-AD groups, similarly associated with non-AD factors and diverging cognitive outcomes. In the autopsy cohort, limbic T-N mismatch correlated with TDP-43 co-pathology. DISCUSSION: T-N mismatch may provide a personalized approach for determining non-AD factors associated with resilience/vulnerability in AD.
|
|
| 3. |
- Xie, Long, et al.
(författare)
-
Tau burden is associated with cross-sectional and longitudinal neurodegeneration in the medial temporal lobe in cognitively normal individuals
- 2022
-
Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:S1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Neurofibrillary tangle pathology is thought to drive neurodegeneration in beta-amyloid positive (A+) cognitively normal (CN) individuals, i.e., preclinical Alzheimer’s disease (AD).However, in beta-amyloid negative (A-) CN, the contribution of tau pathology [primary age-related tauopathy (PART)] to neurodegeneration remains uncertain. We investigate the correlation between tau burden measured by PET in the medial temporal lobe (MTL) and MRI-derived cross-sectional and longitudinal structural atrophy in these cohorts. Methods: 420 CN (A-/A+: 294/101, Table 1) individuals from ADNI with AV1451 PET and T1-weighted MRI acquired within one year were included. Bilateral anterior/posterior hippocampal volume and thickness of entorhinal cortex (ERC), Brodmann areas 35/36 (BA35/BA36) and parahipocampal cortex (PHC) were obtained from baseline MRI scans. Bilateral MTL tau burden was computed as AV1451 uptake across ERC and BA35. Beta-amyloid status was determined with PET by standard cut-offs (Florbetapir: 1.11; Florbetaben: 1.08). In a subset of participants with prospective longitudinal MRI scans (up to 4.5 years), annualized volume change rate of each MTL subregion was estimated. Intracranial volume and MRI follow-up time were additional covariates for cross-sectional and longitudinal analysis respectively. We performed the analysis separately for each hemisphere in the whole CN cohort and its A+ and A- subgroups. Results: Tau burden was significantly associated with cross-sectional left BA35/36 thickness in the whole cohort and bilateral volume in both A+ CN and the whole cohort (Table 2, Figure 1), but not in in A- CN. Stronger correlations between MTL tau burden and longitudinal atrophy, despite smaller sample size, was observed in almost all the MTL subregions regardless of amyloid status (Table 3, Figure 1). In general, effects from the left hemisphere were stronger than those from the right hemisphere. All significant correlations were maintained when corrected for beta-amyloid PET SUVR. Conclusions: The results demonstrated that elevated tau predicts subsequent neurodegeneration in early Braak regions in CN subjects regardless of amyloid status. This indicates that PART may be an important driver of neurodegeneration already during normal ageing in cognitively normal individuals.
|
|
