Related Experiment Video
Updated: Jun 28, 2025
08:29
Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans
Published on: December 18, 2016
14.0K
Multi-pathological contributions toward atrophy patterns in the Alzheimer's disease continuum
Rosaleena Mohanty1, Daniel Ferreira1,2, Eric Westman1,3
1Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Karolinska Institutet, Huddinge, Sweden.
Frontiers in Neuroscience
|April 24, 2024
Summary
Alzheimer's disease (AD) brain atrophy patterns are linked to tau pathology, not amyloid or cerebrovascular burden. Atrophy severity and typicality correlate with cognitive function, highlighting tau's role in AD progression.
Area of Science:
- Neuroscience
- Neuropathology
- Radiology
Background:
- Alzheimer's disease (AD) heterogeneity in brain atrophy is often studied independently concerning amyloid-beta (Aβ), tau pathology, and cerebrovascular burden.
- The specific contribution of each pathology to the observed atrophy patterns remains unclear.
Purpose of the Study:
- To investigate the relationship between Alzheimer's disease (AD) atrophy patterns, defined by typicality and severity, and the underlying pathological hallmarks (Aβ, tau) and cerebrovascular burden.
- To determine how these pathological factors influence cognitive domains.
Main Methods:
- Utilized MRI-derived atrophy measures of typicality (hippocampus to cortical volume ratio) and severity (total gray matter volume) in 149 amyloid-positive (Aβ+) individuals across the AD continuum.
- Employed partial correlation and multiple regression analyses to assess associations between atrophy dimensions, Aβ, tau, cerebrovascular burden, and cognitive scores.
Main Results:
- Atrophy typicality and severity were significantly associated with tau burden (p < 0.001), even after controlling for Aβ and cerebrovascular burden.
- Both typicality and severity correlated with memory, executive function, and language cognitive domains, suggesting better performance in hippocampal sparing and minimal atrophy patterns.
- Tau pathology, but not Aβ or cerebrovascular burden, independently explained cognitive performance beyond atrophy patterns.
Conclusions:
- Atrophy severity in Alzheimer's disease (AD) is more strongly linked to tau burden than typicality, independent of Aβ and cerebrovascular burden.
- Atrophy patterns (typicality and severity) and tau pathology are key determinants of cognitive function in memory, executive function, and language domains.
- These findings underscore the differential impact of tau pathology versus Aβ and cerebrovascular burden on AD heterogeneity and cognitive decline.
Related Concept Videos
01:26Alzheimer's Disease: Overview
468
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
468
01:22Alzheimer's Disease: Treatment
183
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
183
01:15Parkinson's Disease: Overview
537
Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
537
03:03Amyloid Fibrils
9.5K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.5K