Consistent genes associated with structural changes in clinical Alzheimer's disease spectrum

Area of Science:

• Neuroimaging
• Genetics
• Alzheimer's Disease Research

Background:

• Alzheimer's disease (AD) is characterized by widespread neurodegeneration.
• The underlying neurobiological and pathogenic mechanisms of structural atrophy across the AD spectrum are not fully understood.

Purpose of the Study:

• To explore structural brain atrophy across the entire Alzheimer's disease (AD) spectrum.
• To investigate the genetic mechanisms associated with observed structural changes using gene expression data.

Main Methods:

• Utilized structural MRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset.
• Included participants with early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), AD, and normal controls (NC).
• Integrated gene expression data from the Allen Human Brain Atlas.

Main Results:

• Identified significant volume atrophy in the left thalamus, left cerebellum, and bilateral middle frontal gyrus across the AD spectrum.
• Found positive associations between structural changes and genes like ABCA7, SORCS1, and SORL1.
• Observed negative associations with genes such as CD33, PLCG2, and APOE.
• Gene enrichment analysis indicated distinct functional roles for positively and negatively associated genes.

Conclusions:

• The study provides a deeper understanding of the biological mechanisms driving structural changes in prodromal and clinical Alzheimer's disease.
• Findings link specific gene expression patterns to brain atrophy in AD, contributing to knowledge of AD pathogenesis.