Evolving brain structural changes in PSEN1 mutation carriers
Roser Sala-Llonch1, Albert Lladó2, Juan Fortea3
1Department of Psychiatry and Clinical Psychobiology, Universitat de Barcelona, Barcelona, Spain; Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Neurobiology of Aging
|February 2, 2015
Summary
Brain structure changes occur years before Alzheimer's symptoms appear in presenilin 1 mutation carriers. Early increases in brain volume are followed by accelerated loss, suggesting complex disease progression.
Area of Science:
- Neuroscience
- Genetics
- Radiology
Background:
- Familial Alzheimer's disease (AD) offers a unique window into preclinical brain alterations.
- Presenilin 1 (PSEN1) gene mutations are a known cause of early-onset familial AD.
- Understanding presymptomatic brain changes is crucial for early intervention strategies.
Purpose of the Study:
- To investigate structural brain changes in individuals with PSEN1 mutations before symptom onset.
- To compare brain morphology and longitudinal changes between symptomatic carriers, asymptomatic carriers (AMC), and non-carriers.
- To elucidate the nonlinear trajectory of brain structure alterations in the presymptomatic phase of AD.
Main Methods:
- Structural magnetic resonance imaging (MRI) was employed in 38 participants from PSEN1 mutation-carrying families.
- Participants included symptomatic carriers (n=11), asymptomatic carriers (n=13), and non-carriers (n=14).
- A subset underwent longitudinal scanning at 2 and 4 years to assess changes over time.
Main Results:
- Symptomatic carriers exhibited reduced cortical thickness (CTh) and volume in multiple brain regions, with progressive decline.
- Asymptomatic carriers showed increased CTh and volume in temporoparietal regions and precuneus-posterior cingulate at baseline.
- Longitudinal analysis revealed accelerated CTh loss in AMC across several key brain areas, including the precuneus-posterior cingulate.
Conclusions:
- Brain structure in PSEN1 mutation carriers follows nonlinear trajectories, with initial regional increases preceding neurodegeneration.
- These early volumetric changes may be linked to neuroinflammation, amyloid accumulation, or inherent morphometric differences.
- The findings highlight the dynamic nature of brain alterations during the preclinical stages of familial Alzheimer's disease.
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