The impact of the genetic risk factor BIN1 to Alzheimer’s disease development

" Alzheimer’s disease (AD) was identified more than a century ago. Yet, there is still no cure and the mechanisms behind the most common form of AD (late-onset, LOAD) are still an open question. BIN1 was the second gene most frequently associated with LOAD. Bin1 depletion has been linked with AD earliest pathomechanisms: increased beta-amyloid (Aβ) accumulation, endosomal abnormalities, and synaptic defects. Sequencing of BIN1 genomic locus identified regulatory and coding variants of BIN1, indicating that Bin1 correct levels and function are essential for a healthy brain. Two coding variants associated with LOAD (rs754834233, Bin1-PL, and rs138047593, Bin1-KR) lead to missense mutations in Bin1 protein. This work aimed to understand whether LOAD mutations in BIN1 result in Bin1 loss of function and contribute to LOAD early mechanisms. "N/