Biomarkers.

Background: The medial temporal lobe's (MTL) early involvement in tau pathology makes it a key focus in the development of preclinical Alzheimer's disease (AD) biomarkers. ROI analyses in prior studies reported significant MTL structural differences in cognitively normal individuals with and without β-amyloid (A+/-CN). Pointwise analysis, offering spatial information of early neurodegeneration, has potential to pinpoint "signature regions" of pathological change, but has been underexplored in the MTL.

Biomarkers.

Background: The extent to which pathological processes in aging and Alzheimer's disease (AD) relate to functional alterations in the medial temporal lobe (MTL)-dependent brain networks is poorly understood. Here, we examined the relationship between tau accumulation in the (trans)entorhinal cortex and functional connectivity (FC) in two MTL-affiliated brain networks - the Anterior-Temporal (AT) and Posterior-Medial (PM) - in normal agers, individuals with preclinical AD, and patients with symptomatic AD.

Method: In this cross-sectional study, we analyzed data from 125 individuals from the Penn ADRC (Table 1).

Biomarkers.

Background: Previous work suggests functional abnormalities in the human brain in preclinical Alzheimer's disease. However, little has been explored about the relationship between BOLD fMRI signal amplitude/energy over time and AD pathology. In this work we analyzed the effects of AD progression on amplitude of low-frequency fluctuations (ALFF) during resting-state fMRI scans both at the whole-brain level and at a more granular level, focused on regions of the medial temporal lobe (MTL) that are most vulnerable to AD pathology.

Alzheimer's Imaging Consortium.

Background: The extent to which pathological processes in aging and Alzheimer's disease (AD) relate to functional alterations in the medial temporal lobe (MTL)-dependent brain networks is poorly understood. Here, we examined the relationship between tau accumulation in the (trans)entorhinal cortex and functional connectivity (FC) in two MTL-affiliated brain networks - the Anterior-Temporal (AT) and Posterior-Medial (PM) - in normal agers, individuals with preclinical AD, and patients with symptomatic AD.

Method: In this cross-sectional study, we analyzed data from 125 individuals from the Penn ADRC (Table 1).

Alzheimer's Imaging Consortium.

Background: Previous work suggests functional abnormalities in the human brain in preclinical Alzheimer's disease. However, little has been explored about the relationship between BOLD fMRI signal amplitude/energy over time and AD pathology. In this work we analyzed the effects of AD progression on amplitude of low-frequency fluctuations (ALFF) during resting-state fMRI scans both at the whole-brain level and at a more granular level, focused on regions of the medial temporal lobe (MTL) that are most vulnerable to AD pathology.

Alzheimer's Imaging Consortium.

Background: The medial temporal lobe's (MTL) early involvement in tau pathology makes it a key focus in the development of preclinical Alzheimer's disease (AD) biomarkers. ROI analyses in prior studies reported significant MTL structural differences in cognitively normal individuals with and without ß-amyloid (A+/-CN). Pointwise analysis, offering spatial information of early neurodegeneration, has potential to pinpoint "signature regions" of pathological change, but has been underexplored in the MTL.

Tau-neurodegeneration mismatch reveals vulnerability and resilience to comorbidities in Alzheimer's continuum.

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.

Tau-Neurodegeneration reveals vulnerability and resilience to comorbidities in Alzheimer's continuum.

Variability in the relationship of tau-based neurofibrillary tangles (T) and degree of neurodegeneration (N) in Alzheimer's Disease (AD) is likely attributable to the non-specific nature of N, which is also modulated by such factors as other co-pathologies, age-related changes, and developmental differences. We studied this variability by partitioning patients within the Alzheimer's continuum into data-driven groups based on their regional T-N dissociation, which reflects the residuals after the effect of tau pathology is "removed". We found six groups displaying distinct spatial T-N and thickness patterns despite similar tau burden.

Aging and Alzheimer's Disease Have Dissociable Effects on Medial Temporal Lobe Connectivity.

Functional disruption of the medial temporal lobe-dependent networks is thought to underlie episodic memory deficits in aging and Alzheimer's disease. Previous studies revealed that the anterior medial temporal lobe is more vulnerable to pathological and neurodegenerative processes in Alzheimer's disease. In contrast, cognitive and structural imaging literature indicates posterior, as opposed to anterior, medial temporal lobe vulnerability in normal aging.