Presenilin-1-associated abnormalities in regional cerebral perfusion

Area of Science:

• Neuroscience
• Genetics
• Medical Imaging

Background:

• The presenilin-1 (PS-1) gene is implicated in early-onset Alzheimer's disease (AD).
• Understanding the genetic and molecular underpinnings of AD is crucial for early diagnosis and intervention.

Purpose of the Study:

• To investigate the impact of PS-1 gene mutations on regional cerebral perfusion.
• To determine if SPECT imaging can detect early signs of AD in PS-1 mutation carriers before clinical symptoms manifest.

Main Methods:

• SPECT imaging was used to measure cerebral perfusion in 57 individuals from a large South American pedigree with a PS-1 mutation.
• Subjects included cognitively normal non-carriers, asymptomatic PS-1 mutation carriers, and individuals with diagnosed AD.
• Data analysis involved voxel-wise t-tests (t-maps) and singular value decomposition (SVD) for vector score analysis.

Main Results:

• Asymptomatic PS-1 mutation carriers showed reduced perfusion in the hippocampal complex, cingulate cortex, and parietal and frontal lobes compared to controls.
• AD patients exhibited decreased perfusion in the posterior parietal and superior frontal cortex.
• Discriminant function analysis using SVD vector scores accurately classified 86% of subjects across the three groups (p < 0.0005).

Conclusions:

• SPECT imaging can detect regional cerebral perfusion abnormalities in individuals with PS-1 mutations before the onset of clinical AD symptoms.
• These findings highlight the potential of neuroimaging for early AD detection in presymptomatic carriers.