Detecting At-Risk Alzheimer's Disease Cases

Area of Science:

• Neuroscience
• Genetics
• Biomarkers

Background:

• APOEɛ4 is a major genetic risk factor for Alzheimer's disease (AD).
• Amyloid dysmetabolism is an early event predicting clinical AD and a target for intervention.
• Improved identification of individuals at increased AD risk is crucial for secondary prevention trials.

Purpose of the Study:

• To evaluate recruitment procedures for identifying individuals at increased risk for Alzheimer's disease.
• To assess the utility of pathological cerebrospinal fluid (CSF) Aβ42 concentrations (pAβ) and APOEɛ4 genotype as risk markers.

Main Methods:

• A multi-center study in Norway included 490 subjects aged 40-80 years.
• Participants were recruited via advertisements, media, or memory clinics.
• CSF biomarkers (Aβ42) and APOE genotype were analyzed in clinical and cognitive assessments, including MRI.

Main Results:

• Cases (self-referrals and memory clinic referrals) showed higher frequencies of pAβ and APOEɛ4 compared to normal controls (NC).
• Normal controls with first-degree relatives with dementia (NCFD) had higher APOEɛ4 frequencies but not increased pAβ.
• Memory clinic referrals were enriched for pAβ, while self-referred and NCFD cases were often pAβ negative but APOEɛ4 positive, indicating suitability for primary intervention.

Conclusions:

• Memory clinic referrals are suitable for studies targeting amyloid pathology.
• Self-referred and NCFD individuals, particularly those with APOEɛ4, represent a population at risk suitable for primary Alzheimer's disease prevention interventions.