Longitudinal SPECT study in Alzheimer's disease: relation to apolipoprotein E polymorphism

Area of Science:

• Neuroscience
• Genetics
• Medical Imaging

Background:

• Alzheimer's disease (AD) is characterized by progressive cerebral hypoperfusion, initially affecting posterior association cortex and later spreading to the frontal cortex.
• The apolipoprotein E (ApoE) sigma4 allele is a known genetic risk factor for developing Alzheimer's disease.

Purpose of the Study:

• To investigate the impact of apolipoprotein E (ApoE) polymorphism, specifically the sigma4 allele, on regional cerebral blood flow (rCBF) in patients with mild Alzheimer's disease.
• To test the hypothesis that ApoE sigma4 allele carriers with Alzheimer's disease exhibit more severe cerebral hypoperfusion.

Main Methods:

• A longitudinal study involving 31 Alzheimer's disease patients and 8 controls over three years.
• Regional cerebral blood flow ratios (to cerebellum) were assessed using 99mTc-HMPAO SPECT imaging.
• Apolipoprotein E (ApoE) genotypes were determined via PCR and Hha1 restriction enzyme digestion.

Main Results:

• All Alzheimer's disease patients demonstrated bilateral temporoparietal hypoperfusion compared to controls.
• Subgroups carrying the ApoE sigma4 allele showed the most significant hypoperfusion in parietal, occipital, and temporal cortices at baseline and follow-up.
• These ApoE sigma4 subgroups experienced the greatest percentage reduction in cerebral blood flow in temporal and occipital regions.

Conclusions:

• Apolipoprotein E (ApoE) polymorphism plays a role in the pathogenesis and heterogeneity of Alzheimer's disease.
• The presence of the ApoE sigma4 allele is associated with more severe cerebral hypoperfusion in Alzheimer's disease patients.
• These findings suggest potential implications for developing targeted therapeutic strategies for Alzheimer's disease based on genetic profiles.