Bridging Integrator 1 (BIN1) Genotypes Mediate Alzheimer's Disease Risk by Altering Neuronal Degeneration.

Area of Science:

• Neuroscience
• Genetics
• Biomarkers

Background:

• Bridging integrator 1 (BIN1) is a key genetic locus associated with Alzheimer's disease (AD).
• Previous research indicated BIN1 modulates tau pathology in vitro.
• The specific impact of BIN1 on AD biomarkers across the disease continuum remained unclear.

Purpose of the Study:

• To investigate the association between BIN1 genetic loci and AD-specific biomarkers.
• To explore BIN1's role in Alzheimer's disease pathogenesis.
• To assess BIN1's effects on cerebrospinal fluid (CSF) proteins, brain structure, and metabolism.

Main Methods:

• Analysis of 812 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.
• Utilized multiple linear models to assess associations between BIN1 loci and AD biomarkers at baseline and follow-up.
• Included CSF protein levels, MRI-derived brain structures, and Positron Emission Tomography (PET) imaging for glucose and amyloid-beta (Aβ) metabolism.

Main Results:

• BIN1 loci significantly correlated with elevated T-tau and P-tau levels in CSF.
• BIN1 genotypes were strongly associated with hippocampal and parahippocampal atrophy on MRI.
• BIN1 loci showed significant associations with altered glucose metabolism on FDG-PET but not with Aβ deposition on AV45-PET imaging.

Conclusions:

• BIN1 contributes to Alzheimer's disease risk by influencing neurodegenerative processes.
• The study supports BIN1's role in altering tau pathology, brain atrophy, and glucose metabolism.
• BIN1's impact on AD pathogenesis appears independent of amyloid-beta pathology.